Post-transcriptional control

Figure 7-87. Possible posttranscriptional controls on gene expression. Only a few of these controls are likely to be important for any one gene.

Many steps in the pathway from RNA to protein are regulated by cells to control gene expression. Some genes, however, are transcribed at a constant level and turned on and off solely by posttranscriptional regulatory processes. These processes include : (1) attenuation of the RNA transcript by its premature termination, (2) alternative RNA splice-site selection, (3) control of 3 -end formation by cleavage and poly-A addition, (4) RNA editing, (5) control of transport from the nucleus to the cytosol, (6) localization of mRNAs to particular parts of the cell, (7) control of translation initiation, and (8) regulated mRNA degradation.
Most of these control processes require the recognition of specific sequences or structures in the RNA molecule being regulated. This recognition is accomplished by either a regulatory protein or a regulatory RNA molecule.

*Transcription Attenuation Causes the Premature Termination of Some RNA Molecules eg. Bacteria and in HIV (human AIDS virus) *RNA editing -Production of a functional mRNA by insertion or alteration of individual nucleotides in an RNA molecule after it is synthesized. -eg. RNA transcripts that code for proteins in the mitochondria of trypanosomes and plants. -one or more U nucleotides are inserted (or, less frequently, removed) from selected regions of a transcript, causing major modifications in both the original reading frame and the sequence, thereby changing the meaning of the message. -guide RNAs have a 5 end that is complementary in sequence to one end of the region of the transcript to be edited

Figure 7-94. RNA editing in the mitochondria of trypanosomes. Guide RNAs contain at their 3 end a stretch of poly U, which donates U nucleotides to sites on the RNA transcript that mispair with the guide RNA; thus the poly-U tail gets shorter as editing proceeds (not shown). Editing generally starts near the 3 end and progresses toward the 5 end of the RNA transcript, as shown, because the anchor sequence at the 5 end of most guide RNAs can pair only with edited sequences.

Some mRNAs Are Localized to Specific Regions of the Cytoplasm

-If the mRNA encodes a protein that is destined to be secreted or expressed on the cell surface, it will be directed to the endoplasmic reticulum (ER) by a signal sequence at the protein's amino terminus

-In other cases the entire protein is synthesized by free ribosomes in the cytosol, and signals in the completed polypeptide chain may then direct the protein to other sites in the cell.
-Some mRNAs are themselves directed to specific intracellular locations before translation begins. -signals that direct mRNA localization are typically located in the 3 untranslated region (UTR) of the mRNA molecule -RNA localization has been observed in many organisms, including unicellular fungi, plants, and animals, and it is likely to be a common mechanism used by cells to concentrate high-level production of proteins at specific sites.

Proteins That Bind to the 5 and 3 Untranslated Regions of mRNAs Mediate Negative Translational Control
In bacterial mRNAs a conserved stretch of six nucleotides, the ShineDalgarno sequence, is always found a few nucleotides upstream of the initiating AUG codon. This sequence forms base pairs with the 16S RNA in the small ribosomal subunit, correctly positioning the initiating AUG codon in the ribosome. Because this interaction makes a major contribution to the efficiency of initiation, it provides the bacterial cell with a simple way to regulate protein synthesis through negative translational control mechanisms
Eucaryotic mRNAs do not contain a Shine-Dalgarno sequence. Instead, the selection of an AUG codon as a translation start site is largely determined by its proximity to the cap at the 5 end of the mRNA molecule, which is the site at which the small ribosomal subunit binds to the mRNA and begins scanning for an initiating AUG codon.

-vast majority of mRNAs in a bacterial cell are very unstable, having a half-life of about 3 minutes. *degraded by exonucleases in 3 to 5 direction * mRNAs are both rapidly synthesized and rapidly degraded (a bacterium can adapt quickly to environmental changes) -mRNAs in eucaryotic cells are more stable *have half-lives of more than 10 hours (encoding -globin) *have half-lives of 30 minutes or less (often code for regulatory proteins) -production rates need to change rapidly in cells

Two major degradation pathways exist for eucaryotic mRNAs

-sequences in each mRNA molecule determine the pathway and kinetics of degradation

1. gradual shortening of the poly-A tail -most common pathway -in the cytosol, the poly-A tails (which average about 200 As in length) are gradually shortened by an exonuclease that chews away the tail in the 3 to 5 direction.

-critical threshold of tail shortening has been reached (approximately 30 A's remaining) the 5 cap is removed (a process called decapping) and the RNA is rapidly degraded -the proteins that carry out tail-shortening compete directly with the machinery that catalyzes translation -many mRNAs carry in their 3 UTR sequences binding sites for specific proteins that increase or decrease the rate of poly-A tail shortening. 2. begins with the action of specific endonucleases -simply cleave the poly-A tail from the rest of the mRNA in one step (mRNAs that are degraded in this way carry specific nucleotide sequences, typically in their 3 UTR, that serve as recognition sequences for the endonucleases).