Y RNA

Y RNAs are small non-coding RNA components of the Ro ribonucleoprotein particle (Ro RNP). The Ro RNP was first identified by Lerner "et al". as a target of autoimmune antibodies in patients with systemic lupus erythematosus. [cite journal | last = Lerner | first = MR | coauthors = Boyle JA, Hardin JA, Steitz JA | year = 1981 | title = Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. | journal = Science | volume = 211 | pages = 400–402 | pmid = 6164096 | doi = 10.1126/science.6164096]

Function

Two functions have been described for Y RNAs in the literature: In one line of evidence, Y RNA appears to function as a repressor of Ro. In its free state, Ro binds to a variety of misfolded RNAs including misfolded 5S rRNAs, and is thought to act as some sort of quality control mechanism. [cite journal | last = Reinisch | first = KM | coauthors = Wolin SL | year = 2007 | title = Emerging themes in non-coding RNA quality control | journal = Curr Opin Struct Biol. | volume = 17 | pages = 209–214 | pmid = 17395456 | doi = 10.1016/j.sbi.2007.03.012] Crystal structures of Ro complexed either with Y RNA or another RNA showed that Ro binds single-stranded 3' ends of RNAs relatively nonspecifically, whereas Y RNA binds specifically at a second site that regulates access of other RNAs. [cite journal | last = Stein | first = AJ | coauthors = Fuchs G, Fu C, Wolin SL, Reinisch KM | year = 2005 | title = Structural insights into RNA quality control: The Ro autoantigen binds misfolded RNAs via its central cavity | journal = Cell | volume = 121 | pages = 529–537 | pmid = 15907467 | doi = 10.1016/j.cell.2005.03.009] In "Deinococcus", free Ro has also been shown to function in 23S rRNA maturation.cite journal | author = Chen X, Wurtmann EJ, Van Batavia J, Zybailov B, Washburn MP, Wolin SL | title = An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans | journal = Genes Dev. | volume = 21 | issue = 11 | pages = 1328–39 | year = 2007 | pmid = 17510283 | doi = 10.1101/gad.1548207 | issn = ] In "Deinococcus", mutants lacking Y RNA are viable, and Y RNA appears to be unstable except when complexed with Ro.Secondly, it has been described recently that human Y RNAs are functionally required for DNA replication.cite journal | author = Christov CP, Gardiner TJ, Szüts D, Krude T | title = Functional requirement of noncoding Y RNAs for human chromosomal DNA replication | journal = Mol. Cell. Biol. | volume = 26 | issue = 18 | pages = 6993–7004 | year = 2006 | pmid = 16943439 | doi = 10.1128/MCB.01060-06 | issn = ] Biochemical fractionation and reconstitution experiments have established a functional requirement of human Y RNAs for chromosomal DNA replication in isolated vertebrate cell nuclei "in vitro". Specific degradation of human Y RNAs "in vitro", or in intact cells "in vivo", have led to an inhibition of chromosomal DNA replication. Interestingly, mutant human Y RNAs lacking the conserved binding site for Ro60 protein still support DNA replication, indicating that binding to Ro protein and promoting DNA replication are two separable functions of Y RNAs. Another study cite journal |author=Christov CP, Trivier E, Krude T |title=Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation |journal=Br. J. Cancer |volume=98 |issue=5 |pages=981–8 |year=2008 |month=March |pmid=18283318 |doi=10.1038/sj.bjc.6604254 |url=] , has shown that Y RNAs are overexpressed in human tumours and required for cell proliferation.

tructure

These small RNAs are predicted to fold into a conserved secondary structure.

pecies distribution

Presumptive Y RNA and Ro protein homologs have been found in eukaryotes and bacteria.cite journal | author = Teunissen SW, Kruithof MJ, Farris AD, Harley JB, Venrooij WJ, Pruijn GJ | title = Conserved features of Y RNAs: a comparison of experimentally derived secondary structures | journal = Nucleic Acids Res. | volume = 28 | issue = 2 | pages = 610–9 | year = 2000 | pmid = 10606662 | doi = | issn = ] cite journal | author = Perreault J, Perreault JP, Boire G | title = Ro-associated Y RNAs in metazoans: evolution and diversification | journal = Mol. Biol. Evol. | volume = 24 | issue = 8 | pages = 1678–89 | year = 2007 | pmid = 17470436 | doi = 10.1093/molbev/msm084 | issn = ] Humans appear to have four Y RNAs, named hY1, hY3, hY4 and hY5 and also a large number of pseudogenes. "C. elegans" has one, named CeY RNA. [cite journal | last = Van Horn | first = DJ | coauthors = Eisenberg D, O'Brien CA, Wolin SL | year = 1995 | title = Caenorhabditis elegans embryos contain only one major species of Ro RNP | journal = RNA | volume = 1 | pages = 293–303 | pmid = 7489501] The radiation-resistant bacterium "Deinococcus radiodurans" encodes a homolog of Ro called rsr ("Ro sixty related"), and at least four small RNAs accumulate in "Deinococcus" under conditions where rsr expression is induced (UV irradiation); one of these RNAs appears to be a Y RNA homolog. [cite journal | last = Chen | first = X | coauthors = Quinn AM, Wolin SL | year = 2000 | title = Ro ribonucleoproteins contribute to the resistance of Deinococcus radiodurans to ultraviolet irradiation | journal = Genes Dev | volume = 14 | pages = 777–782 | pmid = 10766734]

References

External links

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