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Post-transcriptional control

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Only a few

of these controls are likelyto be important for any onegene.

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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-Aaddition,

(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.

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*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 themessage.

-guide RNAshave a 5 end that is complementary in

sequence to one end of the region of the transcript to be edited

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Guide RNAs

contain at their 3 end astretch of poly U, whichdonates U nucleotides tosites on the RNA transcriptthat mispair with the guideRNA; thus the poly-U tailgets shorter as editingproceeds (not shown).Editing generally startsnear the 3 end andprogresses toward the 5end of the RNA transcript,as shown, because theanchor sequence at the5 end of most guide RNAscan pair only with editedsequences.

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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.

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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 Shine-Dalgarno 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 themRNA molecule, which is the site at which the small ribosomalsubunit binds to the mRNA and begins scanning for an initiatingAUG codon.

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-vast majority of mRNAs in a bacterial cell are very unstable, having ahalf-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 forregulatory proteins)

-production rates need to change rapidly in cells

Two major degradation pathways exist for eucaryoticmRNAs

-sequences in each mRNA molecule determine the pathwayand 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 chewsaway the tail in the 3 to 5 direction.

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-critical threshold of tail shortening has been reached(approximately 30 A's remaining) the 5 cap is removed (aprocess 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 tailshortening.

2. begins with the action of specific endonucleases

-simply cleave the poly-A tail from the rest of the mRNA in onestep (mRNAs that are degraded in this way carry specific nucleotidesequences, typically in their 3 UTR, that serve as recognition sequencesfor the endonucleases).

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