ch 22: post-transcriptional regulation

Gcn2

• yeast stress sensor ____ phosphorylates eIF2 (recruits first tRNA to P site)

• blocks most translation

phosphorylates, Gcn4

yeast stress signal, Gcn2, _____ initiation factors during amino acid starvation leading the ribosome to translate the ____ gene (induces expression of genes for biosynthesis of all amino acids)

transferrin, 3’, mRNA stability

• ____ is an iron chelator that helps scavenge extracellular iron

• translated by iron response elements (IRP/IRE) in ___ UTR which regulate ____

IRP (iron response protein), IRE (iron response element), transferrin mRNA

when iron is low, binding of _____ to ______ stabilizes _____ (3’ UTR) and increases half-life

IRP/IRE (iron response protein/iron response element), transferrin mRNA

when iron is in excess, iron blocks ____ interaction → ____ is degraded

5’, ferritin mRNA

IRP/IRE (iron response protein/element) in ___ UTR regulates translation of _____ in response to iron levels

ferritin

protein that stores excess iron (harmful during iron starvation)

IRP (iron response protein), IRE (iron response element), ferritin mRNA

during iron starvation, ___ binds ___ → blocks translation of ______(5’ UTR)

lyonization

one X is selected at random for inactivation in female embryo cells

Barr body

inactivated X becomes heterochromatic _____

XIST

• noncoding RNA encoded by XIC locus that coats entire X-chromosome it is expressed from

• inactivates genes via DNA methylation and nucleosome modification

• not expressed in normal males

kleinfelder (XXY)

male calico cats are possible if they have ____

pseudoautosomal, pairing, ovaries

• XO women are sterile because genes in the _____ regions of X are not inactivated

• this region is similar in X and Y chromosomes and allows _____ during meiosis

• two copies of genes in this region are required for functional ____

mRNA

carries information from DNA to ribosome

rRNA

structural and function component of ribosome

tRNA

transfers specific amino acids to growing polypeptide chain during translation

ER/TR (telomerase RNA)

template for reverse transcriptase

snRNA (small nuclear RNA)

facilitates mRNA splicing

gRNA (guide RNA)

directs RNA editing in trypanosomes

miRNA (micro RNA)

regulates gene expression

pri-miRNA

transcripts with double stranded step loops that can be processed by Drosha (RNAase III)

pre-miRNA

exported and loaded onto RISC (RNA induced silencing complex) which includes Argonaute and Dicer → cleaved by DICER (RNAase III) → 20-22 ntd miRNAs paired with complements

Argonaute (RNA helicase)

miRNAs are unwound by ___ and the strand non-complementary to target degraded

target RNA

5’-end sequence of miRNA matches _____ and includes degradation or translational repression

Drosha

cleaves pri-miRNA to generate pre-miRNA

Dicer

cleaves pre-miRNA to generate final 22 nt miRNA

siRNA (small interfering RNA)

• processed by Dicer and RISC complex

• silences specific RNA genes (RNAi) by base pairing to the target

• expression of miRNAs using cell specific promoters enables cell specific down-regulation of target gene expression

Onpattro

• first FDA approved RNAi (RNA interference) drug

• reduces level of TTR protein using siRNA

• ATTR is rare genetic disease caused by misfolding of the liver protein transthyretin (TTR)

ApoE

• involved in clearance of VLDL, HDL, chylomicron remnants by liver

• used to target and protect RNAi (RNA interference using siRNA) drugs

RNA silencing machinery (RITS)

siRNA also involved in heterochromatin formation through _____

lncRNA (long noncoding RNA)

includes transcripts from RNA pol I, II, III, RNAs from process introns