Molecular Bio (Exam 3): mRNA Stability & Localization

mRNA instability is due to the action of what?

ribonucleases.

Some __________ are processive, and some are distributive.

exoribonuclease.

Ribonucleases differ in their __________ preference and mode of attack.

substrate.

mRNAs exhibit a wide range of __________-__________.

half-lives.

Differential mRNA stability is an important contributor to mRNA __________ and therefore a spectrum of proteins made in a cell.

abundance.

The concentration of population of molecules when the rate of synthesis and degradation are constant describes __________ __________. (molecular concentration)

steady state.

Eukaryotic mRNAs exist in the form of __________ from their synthesis to their degradation.

mRNPs.

mRNA associates with this changing population of proteins during its nuclear maturation and cytoplasmic life.

ribonucleoprotein particles (RNPs).

mRNA binds to different regulatory proteins largely through ’ and’ _____.

5’ and 3’ UTR.

Some nuclear-acquired __________ __________ have roles in the cytoplasm.

mRNP proteins.

Some nuclear-acquired mRNP proteins have roles in the __________.

cytoplasm.

Messenger RNAs are __________ molecules.

unstable.

Prokaryotic mRNA degradation involves multiple __________.

enzymes.

Prokaryotic mRNA degradation occurs during __________.

translation.

An mRNA that is simultaneously being translated by multiple ribosomes.

polysome (polyribosome).

An mRNA that codes for one polypeptide.

monocistronic mRNA.

The main degradation enzymes work as a complex called the __________, containing RNase E, PNPase, helicase, and other enzymes.

degradosome.

Degradation of bacterial mRNAs is initiated by removal of  __________ from the 5’ terminus by RppH (RNA pyrophospohydrolase).

pyrophosphate.

Degradation of bacterial mRNAs is initiated by removal of a pyrophosphate from the 5’ terminus by __________.

RppH (RNA pyrophosphohydrolase).

Prokaryotic mRNAs are cleaved by __________ ___ (endonuclease) followed by 3’ to 5’ digestion.

RNase E.

Prokaryotic mRNAs are cleaved by RNase E (endonuclease), followed by what direction of digestion?

3’ to 5’.

RNase E (endonuclease) and 3’-5’ exonuclease (PNPase) are enzymes that are components of the __________.

degradosome.

PNPase (exonuclease) cannot degrade double-stranded region unless there is a __________-__________ region that is long enough for staging itself.

single-stranded.

E. coli poly(A) polymerase (PAP) adds 10-40 A’s to 3’ termini of cleaved mRNAs and facilitates their __________.

degradation.

E. coli __________ adds 10-40 A’s to 3’ termini of cleaved mRNAs and facilitates their degradation.

PAP (poly(A) polymerase).

E. coli poly(A) polymerase (PAP) adds 10-40 __’s to 3’ termini of cleaved mRNAs and facilitates their degradation.

A’s.

E. coli mRNA stability varies so dramatically among different mRNAs due to __________ __________ in the 5’ end and translation efficiency.

secondary structure.

E. coli mRNA stability varies so dramatically among different mRNAs due to secondary structures in the 5’ end and __________ efficiency.

translation.

Most eukaryotic mRNA is degraded via two __________-dependent pathways.

de-adenylation.

The modifications at both ends of mRNA (5’ cap and 3’ poly(A) tail) protect it against degradation by __________.

exonucleases.

mRNA decay is initiated by deadenlation catalyzed by __________ __________ (deadenylases).

poly(A) nucleases.

Deadenylation may be followed either by __________ (Dcp1/2 & Lsm1-7) and 5’ to 3’ exonuclease digestion (Xm1) or by 3’ to 5’ exonuclease digestion (exosome).

decapping.

Deadenylation may be followed either by decapping (Dcp1/2 & Lsm1-7) and 5’ to 3’ __________ digestion (Xm1) or by 3’ to 5’ __________ digestion (exosome).

exonuclease.

5’ end and 3’ end are physically __________.

connected.

Deadenylation results in __________ recruitment at the 3’-end, and __________ recruits Dcp1/2 and Xm1.

Lsm1-7.

Deadenylation-__________ decapping can occur.

independent.

The degradation of the nonpolyadenylated histone mRNAs is initiated by 3’ addition of a __________ __________.

poly(U) tail.

Degradation of some mRNAs may be initiated by __________-specific or __________-specific endonucleolytic cleavage.

sequence; structure.

Degradation of some mRNAs may be initiated by sequence-specific or structure-specific __________ cleavage.

endonucleolytic.

An unknown number of mRNAs are targeted for degradation or translational repression by __________.

microRNAs.

Specific ____-elements in an mRNA affect its rate of degradation. They are commonly present in the 3’ UTR.

cis.

Specific cis-elements in an mRNA affect its rate of degradation. They are commonly present in __________.

3’UTR.

What elements can accelerate mRNA decay?

destabilizing elements (DEs).

What elements are common destabilizing elements in mammals, and are bound by components of degradation machinery, eg. exosome, deadenylases, and decapping enzymes.

AREs (AU-rich elements).

What elements occur on some highly stable mRNAs - pyrimidine-rich sequence in 3’ UTR?

stabilizing elements (SEs).

mRNA degradation rates can be altered in response to a variety of __________.

signals.

A cis sequence found in certain mRNAs whose stability or translation is regulated by cellular iron concentration.

iron-response element (IRE).

IRE: __________ sequesters excess cellular iron.

ferritin.

IRE: __________ receptor transports iron inside.

transferrine.

Newly synthesized RNAs are checked for defects via a __________ __________ system.

nuclear surveillance.

Aberrant RNAs are identified and destroyed by an RNA __________ system in the nucleus and the cytoplasm.

surveillance.

The RNA surveillance system is a __________-__________ process.

two-step.

The two steps of the RNA surveillance system is __________ and __________.

identification/tag; destruction.

The nuclear exosome is responsible for the __________ of aberrant RNAs.

destruction.

The nuclear exosome degrades aberrant RNAs in what direction?

3’ to 5’.

The nuclear exosome degrades aberrant RNAs, but also functions in the __________ of normal substrate RNAs.

processing.

What complex recruits the exosome to aberrant RNAs and facilitates its 3’ to 5’ exonuclease acitvity?

TRAMP.

TRAMP complex includes a __________, which is necessary for unwinding secondary structure.

helicase.

TRAMP complex contains __________ that adds a short 3’ oligo(A) tail.

PAP.

What is the short poly(A) tail, generally referring to a stretch of less than 15 adenylates.

oligo(A) tail.

Substrates for TRAMP-exosome degradation include __________ or __________ spliced pre-mRNA and improperly terminated RNA pol II transcripts lacking a poly(A) tail.

unspliced; aberrantly.

Substrates for TRAMP-exosome degradation include unspliced or aberrantly spliced pre-mRNAs and improperly terminated RNA Pol II transcripts lacking a __________ __________.

poly(A) tail.

What is the first translation event for a newly synthesized and exported mRNA to scan it for abnormalities.

Pioneer round of translation.

During the pioneer round of translation, if an abnormality is found, it is tagged for rapid __________.

degradation.

How many types of mRNA defects are detected?

three.

All three systems of mRNA defect detection involve abnormal translation __________.

termination.

What mRNA surveillance system targets mRNAs with premature termination (stop) codons.

non-sense mediated decay (NMD).

Recognition of a termination codon as premature involve unusual 3’ ____ structure or length in many organisms and the presence of downstream EJC in mammals.

UTR.

Recognition of a termination codon as premature involves unusual 3’ UTR structure or length in many organisms and the presence of downstream __________ __________ __________ in mammals.

exon junction complexes (EJC).

What mRNA surveillance system targets mRNAs lacking an in-frame termination codon due to premature transcription termination or mutations and requires a conserved set of SKI proteins.

Nonstop decay (NSD).

What mRNA surveillance system targets mRNAs with stalled ribosomes in their coding regions (secondary structure or rarely used codons can cause stalling).

No-go decay (NGD).

The three mRNA surveillance systems are also used to regulate __________-__________ of normal RNAs.

half-life.