Recommended
Recommended
More Related Content
Similar to RNA METABOLISM II.pdf
Similar to RNA METABOLISM II.pdf (20)
Recently uploaded
Recently uploaded (20)
RNA METABOLISM II.pdf
- 1. MEDICAL BIOCHEMISTRY, FACULTY OF BASIC MEDICAL SCIENCES Post-transcriptional RNA processing ISHAKA AMINU MBBS, PHD.
- 2. ▪ mRNA synthesized and released from DNA template is called primary transcript or heteronuclear RNA (hnRNA) ▪ In mammals this undergoes extensive processing to become mature mRNA ▪ In bacteria translation of mRNA starts even before the completion of transcription ▪ The modifications occur after mRNA is released from RNAP ▪ Include ▪ Endonuclease cleavage ▪ Poly-A tailing ▪ 5’ capping (7-methyl GTP attachment) ▪ Methylation: of N6 of adenine residue and 2’-OH of ribose ▪ Removal of introns ▪ Joining of exons ▪ Other RNAs also undergo post-transcriptional processing, and some result from mRNA processing 11/18/2022 Dr Aminu Introduction Splicing
- 3. 11/18/2022 Dr Aminu ▪ This occurs to remove introns and at the same time exons are joined together (splicing) ▪ The introns removal is by the action of endonucleases ▪ hnRNA MW is 107, while mature RNA 1-2 x 106 ▪ The process is energy requiring ▪ Takes place in the nucleus Endonuclease cleavage
- 4. ▪ 5’ capping is the addition of 7-methyl GTP with the help of triphosphate linkage to form 5’ cap (at the 5’ end of mRNA) ▪ The functions of 5’ capping are to ▪ prevent the action of 5’ exonucleases on the mRNA. ▪ Confer stability to the mRNA ▪ Allows mRNA recognition from other RNAs ▪ Help translocation mRNA from nucleus to cytoplasm ▪ Help in binding of mRNA to ribosome 11/18/2022 Dr Aminu 5’ capping
- 5. 11/18/2022 Dr Aminu ▪ This occurs at 3’ terminus ▪ The 3’ terminus is polyadenylated ▪ The poly-A tail may be 20-250 nucleotides ▪ The tail ▪ protects mRNA from 3’ exonuclease attack ▪ Regulates transcription termination ▪ Regulates mRNA transport ▪ Regulates translation initiation ▪ Controls total amount of translation Poly-A tailing
- 6. 11/18/2022 Dr Aminu Splicing ▪ This is the removal of introns from primary transcript and joining of exons ▪ Creates mRNA with continuous coding sequences ▪ Allows cells to choose protein they will make ▪ Families of related proteins are produced from the same gene in different types of cells ▪ Examples, families of collagen, α-tropomyosin etc ▪ This occurs by alternative splicing Pre-mRNA mRNA Coding segment Introns cut out and exons spliced together 5’ Cap Exon Intron 5’ 1 30 31 104 Exon Intron 105 Exon 146 3’ Poly-A tail Poly-A tail 5’ Cap 5’ UTR 3’ UTR 1 146 Note: introns are excised by spliceosome (contains snRNA)
- 7. 11/18/2022 Dr Aminu Alternate editing of mRNA ▪ Sometimes gene on mRNA can be edited to produce a different protein ▪ In eukaryotes ApoB gene transcribed into mRNA produces 100kDa protein in the liver as ApoB100 ▪ While same gene in intestine produces a 49kDa protein as ApoB48
- 8. 11/18/2022 Dr Aminu Reverse transcription ▪ Reverse transcription is a phenomenon found in retrovirus sub-group of viruses ▪ HIV virus that causes AIDS is one of the retrovirus ▪ These viruses have RNA as their genome ▪ Therefore, use reverse transcriptase or RNA dependent DNA polymerase to make DNA from the RNA ▪ Complementary DNA strand (cDNA) is synthesized from DNA copy of RNA to form double stranded DNA ▪ Thus, genetic information is transferred from RNA to DNA
- 9. 11/18/2022 Dr Aminu Transcription inhibitors ▪ Transcription is inhibited by certain drugs and toxins ▪ The drugs could be anticancer or antibiotics ▪ Inhibitors of transcription have varied mechanisms
- 10. ▪ RNA degradation in eukaryotes is a key modulator of gene expression ▪ It counterbalances the rate of transcription and rapidly eliminate transcripts that are no longer needed ▪ Often RNA that are deemed nonfunctional or aberrant are eliminated ▪ RNA degradation is generally by exoribonucleases in 5’-3’ or 3’-5’ direction ▪ The main exoribonucleases in eukaryotes are Xrn1 (in cytoplasm) and Xrn2 (in nucleus) ▪ The 3’-5’ exoribonuclease activity is in complex called exosome ▪ Specific RNA can be degraded by endonucleases then followed by Xrn1 or exosome activity 11/18/2022 Dr Aminu RNA degradation
- 11. 11/18/2022 Dr Aminu RNA degradation
- 12. 1. Prevention of export of incomplete or intronic RNA from the nucleus ▪ More genes are transcribed in the nucleus than are allowed to be mRNA in the cytosol ▪ The unused mRNAs are degraded in the nucleus or used to make non-coding RNA molecules 2. Prevention of translation of damaged or unwanted RNA in the cytosol ▪ Failed recognition of 5’-cap and poly-A tail prevents translation-initiation machinery ▪ Recognition of defective mRNA 11/18/2022 Dr Aminu Selective RNA degradation