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Small Nucleolar RNA

Explore the world of snoRNAs, from their biosynthesis mechanisms to guiding modifications on rRNAs, influencing gene expression, and their role in human diseases.

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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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