Post-Transcriptional Modifications PDF

WE MAKE DOCTORS Post-Transcriptional modifications Ana Gabriela Colima Fausto, PhD Learning objectives Determine the importance of Post-transcriptional modifications in the flow of genetic information Name and summarize the main post-transcriptional modifications: 5 ’cap addition,...

WE MAKE DOCTORS Post-Transcriptional modifications Ana Gabriela Colima Fausto, PhD Learning objectives Determine the importance of Post-transcriptional modifications in the flow of genetic information Name and summarize the main post-transcriptional modifications: 5 ’cap addition, 3’ polyA tail addition, Splicing, Alternative splicing and RNA editing Detect clinical applications and correlations regarding post-transcriptional modifications RNA processing Gene transcription produces an RNA that is larger than the mRNA found in the cytoplasm for translation. Primary transcript, heterogeneous nuclear RNA (hnRNA), pre-mRNA. Addition of a 5' cap The 5' end of RNA is capped by a methyl guanosine residue, which protects it from degradation Helps the transcript bind to the ribosome during protein synthesis. Addition of a poly(A) tail Addition up to 250 adenine nucleotides (Polyadenylate polymerase) Protection of the mRNA from degradation Highly conserved AAUAAA consensus sequence (polyadenylation signal) near their 3' end. The polyadenylation site is recognized by a specific endonuclease that cleaves the RNA approximately 20 nucleotides downstream  Splicing lntrons are removed and exons are spliced Gained) together to form the mature mRNA Spliceosomes comprise the primary transcript, five small nuclear RNAs (U1, U2, US, and U4/6), and more than 50 proteins  Alternative splicing Change the accessibility of the different splice sites Cell-specific regulation can determine the type of alternate transcript and eventually the protein product produce Allows switching between the production of nonfunctional and functional proteins, membrane-bound protein versus secreted protein AMBOSS GmbH.Transcription.https://amboss.com/. Accessed January 8th, 2025.  RNA editing Changes in RNA sequence after it has been synthesized by RNA polymerase Insertion, deletion and substitution of nucleotides Editing the mRNA will modify the amino acid sequence of the encoded protein. Deamination of cytidine to uridine, adenosine to inosine. RNA editing  Clinical applications Myotonic dystrophy type 1 arises from an expansion of CTG repeats in the 3′UTR of the (DMPK) gene. The disease phenotypes arises because the repeats encode a toxic RNA that forms a hairpin structure, which sequesters key splicing factors. Among these splicing factors, is the muscleblind (MBNL) family of proteins. Cordycepin is a major bioactive agent in Cordyceps militaris, a fungus used in traditional Chinese medicine. It reduces the poly(A) tail lengths of some, but not all, mRNAs. Bibliography Chapter 8 Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. AMBOSS