Chapter 7 Summary

Molecular Cell Biology SCI 231

How many differences are there between one cell type and another?
1. Many processes are common to all cells, and any two cells in a
single organism therefore have many gene products in
common.
2. Some RNAs and proteins are abundant in the specialized cells
in which they function and cannot be detected elsewhere.
3. Studies of the number of different RNAs suggest that, at any
one time, a typical human cell expresses 30-60% of its
approximately 30.000 genes at some level.
4. Although there are striking differences in coding RNAs
(mRNAs) in specialized cell types, they underestimate the full
range of differences in the final pattern of protein production
covalent modifications after synthesis.
A cell can control the proteins it makes by
1. Controlling when and how often a given gene is transcribed
(transcriptional control).
2. Controlling the splicing and processing of RNA transcripts
(RNA processing control).
3. Selecting which completed mRNAs are exported from the
nucleus to the cytosol and determining where in the cytosol
they are localized (RNA transport and localization
control).
4. Selecting which mRNAs in the cytoplasm are translated by
ribosomes (translational control).
5. Selectively destabilizing certain mRNA molecules in the
cytoplasm (mRNA degradation control)
6. Selectively activating, inactivating, degrading, or localizing
specific protein molecules after they have been made
(protein activity control).

Transcription regulators are proteins that recognize specific

sequences of DNA, that are often called cis-regulatory sequences,
because they must be on the same chromosome to the genes they
control. Transcription regulators bind to these sequences, which puts
into a motion a series of reactions that ultimately specify which
genes are to be transcribed and at what rate.

^ Shows how the different base pairs in DNA can be recognized

from their edges without the need to open the double helix. Below,
the binding of a transcription regulator to a specific DNA sequence.

In B, the dimers and heterodimers are held together very weakly;

they exist predominantly as monomers in solution, and yet dimers
are observed on the appropriate DNA sequence. Here, the proteins
are said to bind to DNA cooperatively. Cooperative binding means
that, over a range of concentrations of the transcription regulator,
binding is more of an all-or-none phenomenon than for
noncooperative binding; at most protein concentrations, the cisregulatory sequence is either nearly empty or nearly fully occupied
and rarely is somewhere in between.
How nucleosomes affect the binding of transcription regulators:

Each of theses 5 genes encodes a different enzyme, and all of these

enzymes are needed to synthesize the amino acid tryptophan from
simpler molecules. The genes are transcribed as a single mRNA
molecule, allowing their expression to be coordinated. A cluster of
genes like this is an operon.
When tryptophan concentrations are low, the operon is transcribed.
When it is abundant, the amino acid is imported into the cell and
shuts down the production of the enzymes, which are no longer
needed. This repression of the tryptophan operon happens as
following:
Within the operons promoter is a cis-regulatory sequence (the
tryptophan operator) that is recognized by a transcription
regulator (the tryptophan repressor).
When the regulator binds to this sequence, it blocks access of
RNA polymerase to the promoter, preventing transcription.
The repressor can bind to DNA only if it has also bound several
molecules of tryptophan.

Genes can be switched on by

activator proteins. These
transcriptional activators work
on promoters that are only
marginally able to bind and
position RNA polymerase on
their own. It binds to its cisregulatory sequence on the
DNA and interacts with the RNA
polymerase to help it initiate
transcription. Without the
activator, the promoter fails to do so efficiently.

The Lac operon in E. coli is controlled by both the Lac repressor and
the CAP activator. The Lac operon encodes proteins required to
import and digest the disaccharide lactose. In the absence of
glucose, the bacterium makes cAMP, which activates CAP to switch
on genes that allow the cell to utilize alternative sources of carbon
including lactose. The would be wasteful, however, for CAP to induce
expression of the Lac operon if lactose itself were not present, thus
it shuts off the operon in the absence of lactose.
LacZ, the first gene of the operon, encodes the enzyme Bgalactosidase, which breaks down lactose to galactose and glucose.
When lactose is absent, the Lac repressor binds to a cis-regulatory
sequence, called the Lac operator, and shuts of expression of the

operon. Addition of lactose increases the intracellular concentration

of a related compound, allolactose, which binds to the Lac repressor,
causing it to undergo a
conformational change
that releases its grip on
the operator DNA. When
glucose is absent, cyclic
AMP is produced by the
cell, and CAP binds to
DNA.

Most bacteria have small,

compact genomes, and the cisregulatory sequences that
control the transcription of a
gene are typically located very
near to the start point of
transcription. But there are some
exceptions cis-regulatory
sequences can be located thousands of nucleotide pairs from the
bacterial genes they control. In these cases, the intervening DNA is
looped out, allowing a protein bound at a distant site along the DNA
to contact RNA polymerase. DNA acts as a tether, enormously
increasing the probability that the proteins will collide, compared to
the situation where one protein is bound to DNA and the other is
free in solution.
Gene control region: the whole expanse of DNA involved in
regulating and initiating transcription of a eukaryotic gene. This

included the promoter, where the general transcription factors and

the polymerase assemble, plus all the cis-regulatory sequences to
which transcription regulators bind to control the rate of the
assembly processes at the promoter.
Eukaryotic transcription regulators usually assemble in groups at
their cis-regulatory sequences. Often two or more regulators bind
cooperatively. In addition, a broad class of multisubunit proteins
termed coactivators and co-repressors assemble on DNA with them.
These do not recognize specific DNA sequences themselves, but are
brought to the sequences by the transcription regulators. Often the
protein-protein interactions between transcription regulators and
between regulators and co-activators are too weak for them to
assemble in solution; however, the appropriate combination of cisregulatory sequences can crystallize the assembly of these
complexes on DNA.

Eukaryotic transcription activator proteins direct local alterations in

chromatin structure. Nucleosome remodeling, nucleosome removal,
histone replacement, and certain types of histone modifications
favor transcription initiation. These alterations increase the
accessibility of DNA and facilitate the binding of RNA polymerase
and the general transcription factors.

Transcription activators can act at different steps:

In general, where several factors work together to enhance a

reaction rate, the joint effect is not merely the sum of the
enhancements that each factor alone contributes, but the product.
Transcription activators often exhibit transcriptional synergy, where
several DNA-bound activator proteins working together produce a
transcription rate that is much higher than the sum of their

transcription rates working alone.

Most eukaryotic repressors work on a gene-by-gene basis. Unlike

bacterial repressors, eukaryotic repressors do not directly compete
with the RNA polymerase for access to the DNA, rather they use a
variety of other mechanisms. Although they all ultimately block
transcription by RNA polymerase, eukaryotic transcription
repressors typically act by bringing co-repressors to DNA. 6 ways in

which eukaryotic repressor proteins can operate:

To avoid control regions of different genes from interfering with one
another, several types of DNA elements compartmentalize the
genome into discrete regulatory domains. Barrier sequences
prevent the spread of heterochromatin into genes that need to be
expressed. Insulators prevent cis-regulatory sequences from
behaving disruptively and activating inappropriate genes. They
function by forming loops of chromatin, an effect mediated by
specialized proteins that bind them. The loops hold a gene and its
control region in rough proximity and help to prevent the control
region from spilling over to adjacent regions.

Multiple inputs are integrated at a promoter. Control regions can

respond to many different inputs, integrate this information, and
produce a complex spatial and temporal output as development
proceeds. Multiple sets of transcription regulators, coactivators and
co-repressors can work together to influence transcription initiation
at a promoter.
.

Some of the different mechanisms used to control transcription

regulators inside eukaryotic cells:

Each transcription regulator in an organism contributes to the

control of many genes. Combinational gene control makes it
possible to generate a great deal of biological complexity even with
relatively few transcription regulators. Combinations of a few
transcription regulators can generate many cell types during
development. A decision to make one of a pair of different
transcription regulators (numbered circles) is made after each cell
division. The production of each transcription regulator is assumed
to be self-perpetuating once it has become initiated. In this way,
through cell memory, the final combinational specification is built up
step by step.

Manipulation of transcription regulators can also coax various

differentiated cells to de-differentiate into pluripotent stem cells that
are capable of giving rise to the different cell types in the body,
much like the embryonic stem (ES) cells. By manipulating
combinations of master transcription regulators, cell types and
differentiation pathways can be readily altered.
Even though the control of gene expresssion is combinational, the
effect of a single transcription regulator can still be decisive in

switching any particular gene on or off, simply by completing the

combination needed to maximally activate or repress that gene. A
single transcription regulator can coordinate the expression of many
different genes by completing this combination.

For a proliferating cell to maintain its identity a property called cell

memory the patterns of gene expression responsible for that
identity must be remembered and passed on to its daughter cells
through subsequent cell divisions. Cells have several ways of
ensuring that their daughters remember what kind of cells they
are. The most important is through a positive feedback loop, where
a master cell-type transcription regulator activates transcription of
its own gene, in addition to that of other cell-type-specific genes.
Each time a cell divides, the regulator is distributed to both
daughter cells, where it continues to stimulate the positive feedback
loop, making more of itself each division.

An analysis of gene regulatory circuits reveals that certain simple

types of arrangements (network motifs) are found over and over
again in cells from widely different species:

In vertebrate cells, the methylation of cytosine provides a

mechanism through which gene expression patterns can be passed
on to progeny cells. The methylated form of cytosine has the same
relation to cytosine that thymine has to uracil, and the modification
thus has no effect on base-pairing. DNA methylation in vertebrate
DNA occurs on C nucleotides largely in the sequence CG, which is
base paired to exactly the same sequence (oppositely) on the other
strand of the DNA helix. A simple mechanism permits the existing
pattern of DNA methylation to be inherited directly by the daughter
DNA strands. An enzyme called maintenance methyl transferase acts

preferentiallyonthoseCGsequencesthatarebasepairedwithaCGsequence
thatisalreadymethylated.Asaresult,thepatternofDNAmethylationonthe
parentalDNAstrandservesasatemplateforthemethylationofthedaughter
DNAstrand,causingthispatterntobeinheriteddirectlyfollowingDNA
replication.
BecauseofthewayDNArepairenzymeswork,methylatedCnucleotidestend
tobeeliminatedinthecourseofevolution.Accidentaldeaminationofan

unmethylatedCgivesrisetoU,whichisnotnormallypresentinDNAand
thereforeeasilydetectedandreplaced.DeaminationofmethylatedCformsT,
however,whichisnotdetected,andsomorethanofCGshavebeenlostin
thisway.TheremainingCGsequences
areveryunevenlydistributed,being
extremelydenseinsomeareascalled
CGislands.Theseweresparedbecause
theyremainedunmethylatedinthegerm
line.
<whitelines=CGdinucleotides,red
circles=methylgroup.

Mammaliancellsarediploid,containing
onesetofgenesfromthefatherandone
fromthemother.Theexpressionofa
smallminorityofgenesdependson
whethertheyhavebeeninheritedfrom
thefatherormother:whenthepaternally
inheritedgenecopyisactive,the
maternallyinheritedgenecopyissilent,
orviseversa.Thisiscalledgenomicimprinting.Becauseonlyonecopyofan
imprintedgeneisexpressed,itcanunmaskmutationsthatwouldnormallybe
coveredbytheother,functionalcopy.
TheXchromosomeislargeandcontainsmorethanathousandgenes,whereas
theYchromosomeissmallandcontainslessthan100genes.Mammalshave
evolvedadosagecompensationmechanismtoequalizethedosageofX
chromosomegeneproductsbetweenmalesandfemales.ThecorrectratioofC
chromosometoautosome(nonsexchromosome)geneproductsiscarefully
controlled.Mammalsachievedosagecompensationbythetranscriptional
inactivationofoneofthetwoXchromosomesinfemalesomaticcellsX
inactivation.TwoXchromosomescanthenexistinthesamenucleus,exposed
tothesamediffusibletranscriptionregulators,yetdifferentirelyintheir
expression.

Xchromosomeinactivationisinitiatedandspreadsfromasinglesitenearthe
middleoftheXchromosome,theXinactivationcenter(XIC).Withinthe
XICisatranscribed20.000nucleotideIncRNA(Xist)whichisexpressed
solelyfromtheinactiveXchromosome.XistspreadsfromtheXICoverthe
entirechromosomeanddirectsgenesilencing.
ImprintingandXchromosomeinactivationareexamplesofmonoallelicgene
expression,whereinadiploidgenome,onlyoneofthetwocopiesofageneis
expressed.

Epigeneticinheritance:aheritablealterationinacellororganismsphenotypethat
doesnotresultfromchangesinthenucleotidesequenceofDNA.Theabilityofa
daughtercelltoretainamemoryofthegeneexpressionpatternsthatwerepresentina
parentcellisanexample.

^ Four distinct mechanisms that can produce an epigeneticform of inheritance in an

organism. (A) epigenetic mechanisms that act in cis. A maintenance methylase can
propagate specific patterns of cytosine methylation. A histone modifying enzyme that
replicates the same modification that attracts it to chromatin can result in the
modification being self-propagating. (B) epigenetic mechanisms that act in trans.
positive feedback loops, formed by transcriptional regulators are found in all species
and are probably the most common form of cell memory. Some proteinscan form selfpropagating prions. If these proteins are involved in gene expression, they can
transmit patterns of gene expression to daughter cells.

Post-transcriptional controls operate after RNA

polymerase has bound to the genes promoter and
has begun RNA synthesis, and are crucial for the
regulation of many genes.
RNA splicing, editing, and translation recoding can
also alter the sequence of amino acids in a protein,
making it possible for the cell to produce more
than one protein variant from the same gene.
Transcription attenuation is the premature
termination of transcription. The new RNA chain
adopts a structure that causes it to interact with
the RNA polymerase in a way that aborts its
transcription. When the gene product is required,
the regulatory proteins bind to the nascent RNA
chain and remove the attenuation, allowing the
transcription of a complete RNA molecule.
Riboswitches are
short sequences of
RNA that change their
conformation on
binding specific small
molecules, such as
metabolites. The
resulting conformational change is used
to regulate gene expression. They are
located near the 5 end of mRNAs, and
fold while the mRNA is being
synthetizes, blocking or permitting
progress of the RNA polymerase.

< Alternative RNA splicing: a cell can splice

an RNA transcript differently and thereby make
different polypeptide chains from the same
gene. In some cases, this occurs because there
is an intron sequence ambiguity: the standard
spliceosome mechanism for removing intron
sequences is unable to distinguish between two
or more alternative pairings of 5 and 3 splice
sites, so that different choices are made by
chance on different transcripts. In most cases,
however, RNA splicing is regulated to switch
from the production of a nonfunctional protein
to a functional one.
The regulation of RNA splicing can also generate
different versions of a protein in different cell
types, according on the needs of the cell. It can
be regulated negatively, by a regulatory
molecule that prevents the splicing machinery
from gaining access to a particular splice site,
usually resulting in the use of a secondary splice
site, producing an altered splicing pattern, or
positively.

The 3 end of a eukaryotic mRNA molecule results form an RNA

cleavage reaction that is catalyzed by additional proteins while the
transcript is elongating. A cell can control the site of this cleavage
so as to change the C-terminus of the protein. In many cases, the
alternative cleavage and polyadenylation sites lie within intron
sequences and the pattern of splicing is thereby altered. This can
produce two closely related proteins differing only in the amino acid
sequences at their C-terminal ends.

RNA editing alters the

nucleotide sequences of RNA
transcripts once they are
synthetized and thereby
changes the coded message
they carry. Two principal
types of mRNA editing occur
in animals: the deamination
of adenine to produce
inosine (A to I editing) and
the deamination of cytosine to produce uracil (C to U editing). In the
coding region, they can alter the pairing properties of the bases,
changing the protein or creating a premature stop codon. Edits
outside the coding region can change the pre-mRNA splicing
pattern, the transport of mRNA to the cytosol, the RNA translation
efficiency, or the base-pairing between microRNAs (miRNAs) and
their mRNA targets.

Regulated nuclear transport of mRNA is a mechanism that

deliberately overrides the delay of export of RNA molecules from the
nucleus until processing has been completed, in order to regulate
gene expression.

On order to make progeny virus, entire, unspliced

viral transcripts must be
exported from the
nucleus to the cytosol,
where they are packaged
into viral capsids and
serve as the viral
genome. This large
transcript, as well as
alternatively spliced HIV
mRNAs that the virus
needs to move to the
cytoplasm for protein
synthesis, still carries
complete introns. The
host cells normal block
to the nuclear export of
unspliced rNAs therefore
provides a problem. The
virus overcomes this by
encoding a protein (Rev)
that binds to a specific
RNA sequence located
within a viral intron. It
interacts with a nuclear
export receptor, which
directs the movement of
viral RNAs through nuclear pores into the cytosol despite the
presence of introns.
The regulation of nuclear export by Rev has several important
consequences for HIV growth and pathogenesis. In addition to
ensuring the nuclear export of specific unspliced RNAs, it divides the
viral infection into an early phase (in which Rev is translated from a
fully spliced RNA and all of the intron-containing viral RNAs are
retained in the nucleus and degraded) and a late phase (in which
unspliced RNAs are exported due to Rev function). This timing helps
the virus replicate by providing the gene products in roughly the
order in which they are needed.

The signals in the mRNA that localize it in the cytosol are usually
concentrated in the 3 untranslated region (UTR), the region of RNA
that extends from the stop codon that terminated protein synthesis
to the start of the poly-A tail.
Once an mRNA has been synthetized, one of the most common
ways of regulating the levels of its protein product is to control the
step that initiates translation.

(A) Sequence-specific RNA-binding proteins repress translation of

specific mRNAs by blocking access of the ribosome to the Shine
Dalgarno sequence (orange).
(B) An RNA thermosensor permits efficient translation initiation
only at elevated temperatures at which the stem-loop structure has
been melted.
(C) Binding of a small molecule to a riboswitch causes a major
rearrangement of the RNA, forming a different set of stem-loop
structures. In the bound structure, the ShineDalgarno sequence
(orange) is sequestered and translation initiation is thereby blocked.
(D) An antisense RNA produced elsewhere from the genome basepairs with a specific mrnA and blocks its translation.
One major way eukaryotic cells decrease their overall rate of protein

synthesis is by the phosphorylation of the translation initiation

factor eIF2 by specific protein kinases that respond to the changes
in conditions. eIF2 forms a complex with GTP and mediates the
binding of the methionyl initiator tRNA to the small ribosomal
subunit, which then binds to the 5 end of the mRNA and begins
scanning along the mRNA. When an AUG codon is recognized, the
eIF2 protein hydrolyzes the bound GTP to GDP, causing a
conformational change in the protein and releasing it from the small
ribosomal subunit. The large unit then joins the small one to form a
complete ribosome that begins protein synthesis.
Because eIF2 binds very tightly to GDP, a guanine nucleotide
exchange factor (eIF2B) is required to cause GDP release so that a
new GTP molecule can bind and eIF2 can be reused. The reuse of
eIF2 is inhibited when it is phosphorylated the phosphorylated eIF2
binds to the eIF2B unusually tightly, inactivating eIF2B. There is
more eIF2 than eIF2B in cells, and even a fraction of phosphorylated
eIF2 can trap nearly all of the eIF2B. This prevents the reuse of the

nonphosphorylated eIF2 and greatly slows protein synthesis.

Although 90% of eukaryotic mRNAs are translated beginning with

the firs AUG downstream from the 5 cap, certain AUGs can be
skipped over during the scanning process. Cells can initiate
translation at positions distant from the 5 end of the mRNA using a
specialized RNA sequence called an internal ribosome entry site
(IRES).

Two mechanisms exist for eventually

destroying each mRNA that is made
by the cell. Both begin with gradual
shortening of the poly-A tail by an
exonuclease, which starts as soon as
the mRNA reaches the cytosol. Once
it is reduced to a critical length, the two pathways diverge. On one,
the 5 cap is removed (decapping), and the exposed mRNA is rapidly
degraded form its 5 end. In the other, the mRNA continues to be
degraded from the 3 end.
The 3 UTR sequences are important in controlling mRNA lifetimes,
carrying binding sites for specific proteins that increase of decrease
the rate of poly-A shortening, decapping, or 3 to 5 degradation.
The half-life is also affected by how efficiently the mRNA is
translated. Poly-A shortening and decapping compete directly with
the machinery that translated the mRNA.

Although poly-A shortening controls the half-life of most eukaryotic

mRNAs, some mRNAs can be degraded by a specialized mechanism
that bypasses this step altogether. In these cases, specific nucleases
cleave the mRNA internally, effectively decapping one end and
removing the poly-A tail from the other so that both halves are
rapidly degraded. The mRNAs that are destroyed in this way carry
specific nucleotide sequences, often in the 3 UTRs, that serve as
recognition sequences for these endonucleases. This strategy
makes it especially simple to tightly regulate the stability of these
mRNAs by blocking or exposing the endonuclease site in response
to extracellular signals.
Many of the previously discussed events
take place in protein and nucleic acid
aggregates called processing- or Pbodies, present in the cytosol. Although
many mRNAs are eventually degraded in
P-bodies, some remain intact and are
later returned to the pool of translating
mRNAs. To be rescued in this way,
mRNAs move from P-bodies to another
type of aggregate known as a stress
granule, which contains translation
initiation factors, poly-A-binding protein,
and small ribosomal subunits.
Translation itself does not occur in stress
granules, but mRNAs can become
translation-ready as the proteins bound to them in P-bodies are
replaced with those in stress granules.
A group of short noncoding RNAs carry out RNA interference
(RNAi). RNAs serve as guide RNAs that selectively organize and
bind through base pairing other RNAs in the cell. When the target
is a mature mRNA, the small noncoding RNAs can bind to it and

direct the formation of certain types of repressive chromatin on its

attached DNA template. Three classes of small noncoding RNAs
work in this way:
1. MicroRNAs (miRNAs)
2. Small interfering RNAs (siRNAs)
3. Piwi-interacting RNAs (piRNAs).

miRNAs base-pair with specific mRNAs and fine-tune their

translation and stability. The miRNA precursors are synthetized by
RNA polymerase II and are capped and polyadenylated. Then they
undergo processing, after which miRNA is assembled with a set of
protein to form an RNA-induced silencing complex (RISC), which
seeks out its target mRNAs by searching for complementary
nucleotide sequences. This search is facilitated by Argonaute
protein, a component of RISC, which holds the 5 region of the
miRNA so that it is optimally positioned for base-pairing to another
RNA molecule. Once an mRNA has been bound by an miRNA,
several outcomes are possible:
1. if the base pairing is extensive, the mRNA is cleaved (sliced)
by the Argonaute protein, effectively removing the mRNAs
poly-A tail and exposing it to exonucleases. The RISC is then
released to seek out additional mRNAs.
2. If the base pairing is less extensive, Argonaute does not slice
the mRNA, but translation of the mRNA is repressed and the
mRNA is shuttled to P-bodies where, sequestered from
ribosomes, it eventually undergoes poly-A tail shortening,
decapping and degradation.

ThepresenceofdoublestrandedRNA(usuallyforeign)inthecelltriggersRNAiby
attractingaproteincomplexcontainingDicer,thesamenucleasethatprocesses
miRNAs.ThisproteincleavesthedoublestrandedDNAintosmallfragments,called
smallinterferingRNAs(siRNAs),whicharethenboundbyArgonauteandother
componentsofRISC.OnestrandoftheduplexRNAisthencleavedanddiscarded,
andtheremainingsinglestrandsiRNAdirectsRISCbacktocomplementaryRNA
moleculesproducedbythevirusortransposableelement.Argonautecleavesthese
molecules,leadingtotheirrapiddestruction.
Insomecases,theRNAinterferencemachinerycanalsoselectivelyshutoffsynthesis
ofthetargetRNAs.TheshortsiRNAsproducesbytheDicerproteinarethen
assembledwithagroupofproteins(includingArgonaute)toformtheRITS(RNA
inducedtranscriptionalsilencing)complex.UsingsinglestrandedsiRNAasaguide
sequence,theRITScomplexbindscomplementaryRNAtranscriptsastheyemerge
fromatranscribingRNApolymeraseII.TheRITScomplexattractsproteinsthat
covalentlymodifynearbyhistonesandeventuallydirecttheformationof
heterochromatintopreventfurthertranscriptioninitiation.

piRNAs seek out RNA targets by base-pairing and transcriptionally

silence intact transposon genes and destroy any RNA produced by
them.
Many species of bacteria use a repository of small noncoding RNA
molecules to seek out and destroy the DNA of the invading viruses.
Many features of this defense mechanism, known as the CRISPR
system, resemble that of miRNAs and siRNAs, but there are 2
important differences:
1. When bacteria are first infected by a virus, they have a
mechanism that causes short fragments of that viral DNA to
become integrated into their genomes. These serve as
vaccinations, in the sense that they become templates for
producing small crRNAs (CRISPS RNAs) that will thereafter
destroy the virus.
2. The crRNAs then become associated with special proteins that
allow them to seek out and destroy double-stranded DNA
molecules.

Long noncoding RNA (lncRNAs) can serve as scaffolds, bringing

together proteins that function in the same process. RNAs can fold
into specific 3D structures that are often recognized by proteins.
In addition to serving as scaffolds, lncRNAs can, through formation
of complementary base pairs, localize proteins to specific sequences
on RNA or DNA molecules.
In some cases, lncRNAs act only in cis, for example when RNA is
held in place by RNA polymerase. Others diffuse from their sites of

synthesis and act in trans.