splicing regulation and variation Flashcards
what is splice site choice regulated through?
trans-acting splicing factors that bind toxic-acting splicing regulatory elements
what are the 4 types of regulatory elements?
Exonic splicing enhancers (ESE)
Exonic splicing silencers (ESS)
Intronic splicing enhancers (ISE)
Intronic splicing silencers (ISS)
waht are examples of proteins that bind to the regulatory elements?
ESE - SR proteins
ESS - hnRNPs
ISS - PTB
what does collagen Q do?
Anchors acetylcholinesterase to the muscle cell membrane at the neuromuscular joint
Has 3 subunits
what does acetylcholinesterase do?
regulating length of signaling between nerve cells and muscle cells by breaking down the signaling protein acetylcholine
waht is the correct expression of COLQ?
he action of a serine arginine splicing factor SRSF1 acting as an ESE. it binds to GGAGG and enchamces binding of U1.
if GGAGG is mutated to GGGGG in COLQ what happens?
SRSF1 can no longer bind and is replaced by hnRNPH which acts as an ESS
what is alternative splicing?
Processing of identical transcripts in a different ways in different cells which can lead to mature mRNAs with different combinations of exons and thus result in different polypeptides
what are the characteristics of alternative splicing?
Produces different proteins from a single gene
Expands genetic diversity
Allows expression of select transcripts in developmental stage or tissue specific manner
Inappropriate control can contribute to disease onset and severity
Can include or exclude exons
Can be used at 3’ or 5’
what is the act of alternative splcing in non-neuronal cells?
PTB binds to intronic silencer sequences on either side of the N1 exon and prevents it form joining the final mature mRNA.
what is the act of alternative splcing in neuronal cells?
PTBP2 binds to the same elements. This binding activates an enhancer sequence that stimulates N1 splicing through binding to the Fox 1 and Fox 2 proteins so N1 can be in the final mRNA
what are the 2 classes of exons?
Constitutive - must be included in the final mRNA
Regulated - can be included or not
what are the characteristics of alternative processing?
Different promoters can be used
Exons can be included or excluded
Different poly(A) processing sites can be used
what are the 2 best exampls of using alternative promoters and alternative polyadenylation?
calcitonin and CGRP and tropomyosin
what are 2 other forms of splicing?
minor or U12 dependent and Cis v trans
