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Small Nucleolar RNA

Small Nucleolar RNA. Megan Salt BMS 265 – Macromolecules Special Topics in Nucleic Acids. Discovery of snoRNAs. U3 snoRNA. First snoRNA found in late 1960’s (U3) Band representing sn and snoRNAs seen from rat nuclei High uridine content led to naming convention. Wikipedia.

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Small Nucleolar RNA

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  1. Small Nucleolar RNA Megan Salt BMS 265 – Macromolecules Special Topics in Nucleic Acids

  2. Discovery of snoRNAs U3 snoRNA • First snoRNA found in late 1960’s (U3) • Band representing sn and snoRNAs seen from rat nuclei • High uridine content led to naming convention Wikipedia

  3. There are several mechanisms of snoRNA biosynthesis • Yeast snoRNAs are generally monocistronic • Plants generate polycistronic snoRNAs • Vertebrate snoRNAs are often within introns of rRNA processing genes Monocistronic Polycistronic Intronic

  4. There are several mechanisms of snoRNA biosynthesis • Polycistronic and intronic snoRNAs require further processing to function Endonucleases 5’ 3’ Exonucleases Splicing machinery

  5. snoRNAs mediate the modification of other RNA nucleotides 2’-O-methylation • Human 18S, 5.8S, and 28S rRNAs contain 110 2'-O-methyl groups and almost 100 pseudouridines • snoRNAs direct methyltransferase and pseudouridinesynthase enzymes to the appropriate rRNA nucleotide Pseudouridylation

  6. snoRNAs act to guide nucleotide modifying enzymes to the proper rRNA site • Antisense elements dictate where the modifications are catalyzed • Target sequences have been confirmed also in snRNAs, as well as mRNAs Filipowicz et al. 2002

  7. snoRNAs function as part of a ribonucleoprotein complex Filipowicz et al. 2002

  8. Evolution of snoRNAs • Enzymes likely evolved from gene duplications of tRNA or rRNA processing enzymes • Ancestral snoRNAs likely guided these enzymes and acquired specificities for novel rRNA sites Lafontaine et al. 1998.

  9. snoRNAs can be used as a biological tool • (1) snoRNA localization elements have been utilized to direct new RNA sequences to the nucleolus • (2) snoRNAs have been used to direct nucleotide modifications to new sites in rRNA via the expression of snoRNAs containing novel guide sequences

  10. snoRNAs have been implicated in human disease • HBII-52 snoRNA involved in modification of serotonin receptor mRNA • Loss of either the paternal or maternal copy of this region leads to two neurological disorders: Prader-Willi or Angelman syndrome, respectively

  11. QUESTIONS??

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