Lecture 23.docx - Lecture 23/24 RNA Processing I II Maturation of nascent transcripts must occur to form functional mRNAs Precursors mRNAs(pre-mRNA are

Lecture 23.docx - Lecture 23/24 RNA Processing I II...

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Lecture 23/24: RNA Processing I & II Maturation of nascent transcripts must occur to form functional mRNAs Precursors mRNAs (pre-mRNA) are modified at their 5' end. A 7-methylguanylate cap is added to the 5' terminal nucleotide through an unusual 5'-5' linkage. In animal cells and in higher plants, the 2' hydroxyl of the ribose group of the first base is methylated. In vertebrates, the second base is also methylated. Addition of the cap: o Protects the pre-mRNA from degradation o Facilitates nuclear export o Recognition by translation factors Proteins bind to RNA through specific domains RNA + Protein = Ribonucleoprotein complex (RNP) Proteins can bind RNA and have specific structural domains that can be recognized. The most common form of RNA binding protein domain is the RNA recognition motif (RRM). Many of the RBP have one or more RRM which catalyzes the interaction between protein and RNA. Sex-lethal can regulate splicing of specific RNAs. It is involved in sex determination in fruitflies, hence its name. The RRM wrap themselves around the pre-mRNA. Polypyrimidine tract binding protein (PTBP) can bind to A-rich or pyrimidine-rich tract of RNA.
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Other RNA binding domains: KH domain, RGG repeats. From pre-mRNA to mRNA: splicing Unlike bacterial genes, eukaryotic genes can (and most of them do) have introns. Exons are those regions of a transcript that are present in the mature mRNA, whereas introns get spliced out from the primary RNA transcript and are not part of the mature mRNA. There can be transcriptional control elements that are nested within the introns. Introns are not junk - they can encode regulatory information. Introns are more frequent and generally longer in higher eukaryotes. Upon the initiation of transcription the 5' end of the emerging pre-mRNA is modified Capping is mediated by a capping enzyme that binds to phosphorylated Ser5. Its activity is enhanced following binding. Because of the pause that occurs before Ser2 phosphorylation, transcription elongation will be delayed until the 5' end of the pre-mRNA is protected.
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Transcription and RNA processing are tightly coupled. The CTD acts as a scaffold for a large number of factors involved in RNA maturation The CTD is critical for: o Capping o Splicing o Polyadenylation o Export of mRNA The CTD regulates the activity of Pol II and ensures that the pre-mRNA are getting processed as they are being transcribed. Introns toward the 5' end of the pre-mRNA are getting spliced out while the 3' end are still being transcribed. CTD acts as a scaffold for the recruitment of processing factors. Introns: Genes in pieces Introns were discovered, because there is a discrepancy between mRNA size and gene size.
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