BBMB 405 1st Edition Lecture 31 Outline of Last Lecture XV Chapter 29 RNA synthesis and Processing C Transcription in eukaryotes is highly regulated con t Outline of Current Lecture XV Chapter 29 RNA synthesis and Processing C Transcription in eukaryotes is highly regulated con t D The discovery of catalytic RNA was revealing in regard to both mechanism and evolution Current Lecture XV Chapter 29 RNA synthesis and Processing C Transcription in eukaryotes is highly regulated con t 1 mRNA editing can change protein sequence a Adenosine deaminases that act on RNA ADAR enzymes deaminate adenosine b ADAR recognizes specific A and catalyzes its conversion to Inosine c Reads out as G instead of A d Adenosine deaminase acting on RNA ADAR unedited version allows Ca2 into ion channel but with single substitution A to I converting Gln to Arg Ca2 is blocked from the channel this has a strong effect on the function of the protein 2 Cytidine deamination can introduce stop codons a C U deamination is catalyzed by APOBEC1 These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute Apolipotrotein B mRNA editing enzyme 1 Expressed in small intestine not in liver b ApoB 100 is synthesized in the liver Transport of synthesized lipids Can bind to LDL receptors c ApoB 48 is synthesized in the small intestine Transport of dietary fats Present in chylomicrons d 3 Pre mRNAs contain intros that are spliced discovered because sequences present in DNA but not in protein 4 Chemistry of splicing transesterfication a b c d Transesterifcation alcohol attack ester and replace R groups no 3 end so use 2 hydroxyl of adenosine found in intron e Mg ions activate nucleophiles 2 OH or 3 OH stabilize leaving groups phosphates f RNA important in this reaction 5 Spliceosome is composed of snRNPs a b snRNPs are present in nucleolus not U3 because it is a snoRNA separate nuclear from nucleolus RNA c Subunits make up sliceosome 6 Process a U1snRNP bound to 5 ss b Spliceosome assembly and action c RNA makes RNA use for scaffold or sequence specific recognition d Structures can be formed between U4 and U6 which needs to be melted prior to activation because U6 needs to form interaction with U2 e U2 and U6 complex coordinates pre mRNA substrates and catalyzes splicing f U6 coordinates metal ions for splicing g U6 U5 U2 complex is recycled 7 When does all of this processing occur a Prior to export from nucleus b Pre mRNA processing occurs co transcriptional c Capping splicing and poly adenylation factors interact with transcription elongation complex d Dependent on phosphorylation state of Pol II C terminal tail e 8 Splicing defects and disease a Human hemoglobin beta chain b Leads to thalassemia hereditary anemia patient has to have one blood transfusion per month c Mutations affecting splicing have been estimated to cause at least 15 of all genetic diseases 9 Alternative splicing a Alternative splicing can produce multiple isoforms b Highly regulated through trans acting protein factors bind and cis regulatory elements within RNA itself c Example CGRP and Calcitonin have different functions D The discovery of catalytic RNA was revealing in regard to both mechanism and evolution 1 Self splicing versus spliceosomal splicing a Self splicing don t require spliceosome RNA that fold into structure and bring together ends of introns b Group I first step catalyzed by free nucleotide so no looped intermediate c Group II catalyzes exact reaction of spliceosome 2 Origin of Life an RNA world This may or may not have been how life started
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