BSCI 331: Exam 3 - Regulation of Protein Translation

untranslated regions (UTRs)

• information in 5’ and 3’ ends able to regulate translation efficiency as well as mRNA stability

• block ribosome from translating RNA

• 5’ utr RNA structure allow binding of translation repressor protein that blocks ribosome access where rna structure itself may inhibit ribosome scanning

• repressors binding to 3’ utr can prevent communication bettween 5’ and 3’ ends of mrna → required for efficient translation initiation

riboswitch

• may use binding of an ion or small molecule to switch between translation as “on” and “off” states ONLY at the 5’ end of mRNA

eIF2 (phosphorylation)

• initiation factor that binds to met-tRNA to become active once have gtp

• inhibits global protein synthesis where unfolded protein is made

• uses GTPase motif to mediate binding of initiator met-tRNA to small ribosomal subunit

eIF2B

• GEF limiting factor that catalyzes exchange of GDP for GTP → activates eIF2

• phosphorylation of eIF2 then turns it into an inhibitor of eIF2B → blocks translation initiation and allow cell to recover

• bounds to eIF2 complex in order to release GDP and add GtP onto eIF2 to make it be active to inhibit or prevent translation to happen

how much of eIF2 do we need for phosphorylation?

only small amount to be phosphorylated to allow for cell recovery

upstream open reading frames (uORFs)

• context surrounding AUG can allow regulation by this

• reading frame must be kept the same throughout

• sequence starting with AUG starting codon and ending with a stop codon, theoretically able to encode a polypeptide (small and short)

• does not mean it will go all the way through translation pathway and reach main coding sequence → eventually will release or cleave off towards middle

• if reach to main coding sequence then able to bind to eIF2

what happens if the ribosome begins to translate a uORF?

• it will terminate with the stop codon and fall off the mRNA before reaching the main coding sequence → only will “scan through” and not necessarily reading it to selectively increase a few proteins during stress conditions such as amino acid starvation

• eIF2 turns decreases global translation initiation that allows some ribosomes to “read through” uORFs to reach the main coding sequence

ATF4

transcription factor involved in responses to various stresses

what happens to atf4 under non stress conditions?

translation of atf4 is inhibited by uORFs

what happens to atf4 under stress conditions?

eIF2 gets phosphorylated which reduces initiation at uORFs (“scan through”)

internal ribosome entry site (IRES)

• allow ribosomes to skip the first AUG codon by binding to an internal site → internally initiates translation

• allows two different protein sequences to be derived from a single mRNA

• may sit between two separate ORFs, allows independent simultaneous translation of two completely different proteins from one mRNA

• different initiation sites may lead to skipping of a signal sequence (required for secreted/transmembrane proteins), and so switching between cytosolic and secreted forms of a protein