Gene Expression and its control- BIOS5010 Lecture 10: mRNA stability

Flashcards covering key vocabulary and concepts from the lecture on mRNA stability, including mRNA processing, degradation pathways, and surveillance mechanisms.

Gene expression

The process from DNA to RNA to protein, involving replication, transcription, and translation.

mRNA processing

mRNA produced from RNA-PolII needs to be spliced, capped, and transported for translation, stabilized by RNAs and proteins.

Pre-mRNA vs Mature mRNA

Pre-mRNA is found only in the nucleus, whereas mature mRNA is used for translation in the cytoplasm.

Three main stages of RNA processing

5’capping, RNA splicing (removal of introns), and 3’poly-adenylation.

5’ and 3’ Untranslated Regions (UTRs)

Sequences upstream and downstream from the coding region of an mRNA that influence mRNA stability, translation, and localisation.

Prokaryotic vs. Eukaryotic mRNA Structure

Prokaryotic mRNA is not altered after transcription, whereas eukaryotic mRNA is capped and polyadenylated.

mRNA instability

mRNA instability is due to the action of ribonucleases which cleave RNA at either internal sites (endoribonucleases) or remove terminal ribonucleotides (exoribonucleases)

Prokaryotic mRNA Degradation Initiation

In prokaryotes, mRNA degradation is initiated by removal of a pyrophosphate from the 5′ triphosphate cap by RppH, stimulating endonuclease RNaseE activity.

The RNA degradosome in bacteria

Includes an endoribonuclease (RNase E), a 3'→5' exonuclease (polynucleotide phosphorylase (PNPase)), DEAD-box RNA helicase, and the glycolytic enzyme enolase.

Capping and poly-A tails

Modified ends of mRNA that increase stability.

5’ cap

Formed by adding a G to the transcript's first base via a 5′–5′ link during mRNA transcription by RNA-PolII.

Function of cap structure in mRNA stability

Protects the mRNA from degradation, influences splicing, export, translation, and recruits translation initiation factors.

3’ Ends of mRNAs

Generated by cleavage followed by polyadenylation (poly-A), protects from degradation, and the sequence AAUAAA signals cleavage.

Eukaryotic mRNA degradation

Most eukaryotic mRNA degradation is triggered by de-adenylation from 3’UTRs, followed by decapping at the 5’ end of mRNA

Deadenylation-Dependent Pathways

Two major mRNA decay pathways initiated by deadenylation, followed either by decapping and 5′ to 3′ exonuclease digestion or 3′ to 5′ exonuclease digestion.

5’ to 3’ mRNA Degradation Pathway

Deadenylation triggers decapping at the 5’ end by Dcp1 and Dcp2, yielding a 5’ monophosphorylated RNA end, a substrate for the exonuclease Xrn1.

3’ to 5’ mRNA Degradation Pathway

Deadenylation is followed by 3’ to 5’ exonuclease digestion by the Exosome complex.

Nuclear mRNA surveillance by the TRAMP- complex

Recognises RNAs that should be degraded, including unspliced pre-mRNAs and improperly terminated RNA Pol II transcripts lacking a poly(A) tail.

Cytoplasmic Surveillance Systems

Nonsense Mediated Decay (NMD), Non Stop Decay (NSD), and No Go Decay (NGD).

Nonsense Mediated Decay (NMD)

Targets mRNAs that contain a premature termination codon (PTC).

NMD mechanism: How are PTC’s recognised?

PTC recognition by downstream exon junction complex (EJC) or mRNA having a too long 3’ UTR.

mRNA localisation

Controls localized translation into protein product during development, cell division, cell migration and cell morphogenesis.