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Ribonucleases differ in their substrate preference and mode of attack. MRNAs exhibit a wide range of half-lives. Some nuclear-acquired mRNP proteins have roles in the cytoplasm.
Ribonucleases differ in their substrate preference and mode of attack. MRNAs exhibit a wide range of half-lives. Some nuclear-acquired mRNP proteins have roles in the cytoplasm.
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Ribonucleases differ in their substrate preference and mode of attack. MRNAs exhibit a wide range of half-lives. Some nuclear-acquired mRNP proteins have roles in the cytoplasm.
Copyright:
Attribution Non-Commercial (BY-NC)
Verfügbare Formate
Als PDF, TXT herunterladen oder online auf Scribd lesen
22.2 Messenger RNAs Are Unstable Molecules mRNA instability is due to the action of ribonucleases. Ribonucleases differ in their substrate preference and mode of attack. endoribonuclease (endonuclease) A ribonuclease that cleaves an RNA at internal site(s). exoribonuclease (exonuclease) A ribonuclease that removes terminal ribonucleotides from RNA. llgure 22.02 22.2 Messenger RNAs Are Unstable Molecules processive (nuclease) An enzyme that remains associated with the substrate while catalyzing the sequential removal of nucleotides. distributive (nuclease) An enzyme that catalyzes the removal of only one or a few nucleotides before dissociating from the substrate. mRNAs exhibit a wide range of half-lives. llgure 22.03: MeLhod for deLermlnlng m8nA half-llves. 22.2 Messenger RNAs Are Unstable Molecules mRNA decay mRNA degradation, assuming that the degradation process is stochastic. Differential mRNA stability is an important contributor to mRNA abundance and therefore the spectrum of proteins made in a cell. steady state (molecular concentration) The concentration of population of molecules when the rates of synthesis and degradation are constant. 22.3 Eukaryotic mRNAs Exist in the Form of mRNPs from Their Synthesis to Their Degradation mRNA associates with a changing population of proteins during its nuclear maturation and cytoplasmic life: ribonucleoprotein particles (RNPs). Some nuclear-acquired mRNP proteins have roles in the cytoplasm. A very large number of RNA-binding proteins (RBPs) exist, most of which remain uncharacterized. Different mRNAs are associated with distinct, but overlapping, sets of regulatory proteins, creating RNA regulons. 22.4 Prokaryotic mRNA Degradation Involves Multiple Enzymes Prokaryotic mRNA degradation occurs during translation. polyribosome (or polysome) An mRNA that is simultaneously being translated by multiple ribosomes. monocistronic mRNA mRNA that codes for one polypeptide. The main degradation enzymes work as a complex called the degradosome. 22.4 Prokaryotic mRNA Degradation Involves Multiple Enzymes Degradation of bacterial mRNAs is initiated by removal of a pyrophosphate from the 5! terminus. Monophosphorylated mRNAs are degraded during translation in a two-step cycle involving endonucleolytic cleavages (endonuclease such as RNase E), followed by 3! to 5! digestion (3-5 exonuclease such as PNPase) of the resulting fragments. llgure 22.03: uegradauon of bacLerlal m8nAs. 22.5 Most Eukaryotic mRNA is Degraded via Two Deadenylation-Dependent Pathways The modifications at both ends of mRNA protect it against degradation by exonucleases: 5 cap & 3 poly(A) tail poly(A) binding protein (PABP) The protein that binds to the 3! stretch of poly(A) on a eukaryotic mRNA. 22.5 Most Eukaryotic mRNA is Degraded via Two Deadenylation-Dependent Pathways The two major mRNA decay pathways are initiated by deadenylation catalyzed by poly(A) nucleases (deadenylases). Deadenylation may be followed either by decapping and 5! to 3! exonuclease digestion or by 3! to 5! exonuclease digestion. llgure 22.06: 1he ma[or deadenylauon-dependenL decay paLhways ln eukaryoLes. 22.5 Most Eukaryotic mRNA is Degraded via Two Deadenylation-Dependent Pathways The exosome, which catalyzes 3! to 5! mRNA digestion, is a large, evolutionarily conserved complex. Degradation may occur within discrete cytoplasmic particles called processing bodies (PBs). A variety of particles containing translationally repressed mRNAs exist in different cell types. maternal mRNA granules Oocyte particles containing translationally repressed mRNAs awaiting activation later in development. neuronal granules Particles containing translationally repressed mRNAs in transit to final cell destinations. stress granules Cytoplasmic particles, containing translationally inactive mRNAs, that form in response to a general inhibition of translation initiation. 22.6 Other Degradation Pathways Target Specific mRNAs Deadenylation-independent decapping proceeds in the presence of a long poly(A) tail ! processes after decapping are similar to those in deadenylation-dependnet pathway. llgure 22.08 22.6 Other Degradation Pathways Target Specific mRNAs The degradation of the nonpolyadenylated histone mRNAs is initiated by 3! addition of a poly(U) tail. llgure 22.08 22.6 Other Degradation Pathways Target Specific mRNAs Degradation of some mRNAs may be initiated by sequence-specific or structure-specific endonucleolytic cleavage. llgure 22.08 22.6 Other Degradation Pathways Target Specific mRNAs An unknown number of mRNAs are target for degradation or translational repression by microRNAs. llgure 22.08 22.6 Other Degradation Pathways Target Specific mRNAs llgure 22.09: 1able summarlzlng key elemenLs of m8nA decay paLhways ln eukaryouc cells. 22.7 mRNA-Specific Half-Lives Are Controlled by Sequences or Structures within the mRNA Specific cis-elements in an mRNA affect its rate of degradation: most common in 3UTR. Destabilizing elements (DEs) can accelerate mRNA decay, while stabilizing elements (SEs) can reduce it. AU-rich elements (AREs) are common destabilizing elements in mammals, and are bound by a variety of proteins. Some DE-binding proteins interact with components of the decay machinery and probably recruit them for degradation. Stabilizing elements occur on some highly stable mRNAs. mRNA degradation rates can be altered in response to a variety of signals. 22.7 mRNA-Specific Half-Lives Are Controlled by Sequences or Structures within the mRNA llgure 22.10: Mechanlsms by whlch desLablllzlng elemenLs (uLs) and sLablllzlng elemenLs (SLs) funcuon. 22.7 mRNA-Specific Half-Lives Are Controlled by Sequences or Structures within the mRNA iron-response element (IRE) A cis sequence found in certain mRNAs whose stability or translation is regulated by cellular iron concentration. llgure 22.11: 8egulauon of Lransferrlng m8nA sLablllLy by lron levels. 22.8 Newly Synthesized RNAs Are Checked for Defects via a Nuclear Surveillance System Aberrant RNAs are identified and destroyed by an RNA surveillance system In the nucleus and the cytoplasm. The nuclear exosome functions both in the processing of normal substrate RNAs and in the destruction of aberrant RNAs. The yeast TRAMP complex recruits the exosome to aberrant RNAs and facilitates its 3! to 5! exonuclease activity. 22.8 Newly Synthesized RNAs Are Checked for Defects via a Nuclear Surveillance System oligo(A) tail a short poly(A) tail, generally referring to a stretch of less than 15 adenylates. Substrates for TRAMP-exosome degradation include unspliced or aberrantly spliced pre-mRNAs and improperly terminated RNA Pol II transcripts lacking a poly(A) tail. llgure 22.12: 1he role of 18AM and Lhe exosome ln degradlng aberranL nuclear 8nAs. 22.9 Quality Control of mRNA Translation Is Performed by Cytoplasmic Surveillance Systems Three types of mRNA defects are detected; all three systems involve abnormal translation termnation. release factor (RF) A protein required to terminate polypeptide translation to cause release of the completed polypeptide chain and the ribosome from mRNA. 22.9 Quality Control of mRNA Translation Is Performed by Cytoplasmic Surveillance Systems Nonsense-mediated decay (NMD) targets mRNAs with premature stop codons. Recognition of a termination codon as premature involves unusual 3! UTR structure or length in many organisms and the presence of downstream exon junction complexes (EJC) in mammals. NMD requires Upf and Smg proteins. pioneer round of translation The first translation event for a newly synthesized and exported mRNA. 22.9 Quality Control of mRNA Translation Is Performed by Cytoplasmic Surveillance Systems llgure 22.14: 1wo mechanlsms by whlch a Lermlnauon codon ls recognlzed as premaLure. llgure 22.13: SubsLraLes for cyLoplasmlc survelllance sysLems. 22.9 Quality Control of mRNA Translation Is Performed by Cytoplasmic Surveillance Systems Nonstop decay (NSD) targets mRNAs lacking an in frame termination codon due to premature transcription termination and requires a conserved set of SKI proteins. No-go decay (NGD) targets mRNAs with stalled ribosomes in their coding regions. llgure 22.13: SubsLraLes for cyLoplasmlc survelllance sysLems. 22.10 Some Eukaryotic mRNAs Are Localized to Specific Regions of a Cell Localization of mRNAs serves diverse functions in single cells and developing embryos. llgure 22.16: 1hree maln funcuons of m8nA locallzauon. 22.10 Some Eukaryotic mRNAs Are Localized to Specific Regions of a Cell Localization requires (1) cis- elements on the target mRNA, (2) trans-factors to that attach mRNA to motor protein, (3) trans-factors repressing translation, and (4) an anchoring system at the destination. zipcode (in RNA) Any of the number of RNA cis elements involved in directing cellular localization. llgure 22.17: Locallzauon of Ash1 m8nA.