title: Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing.
abstract: C/D box small nucleolar RNAs (SNORDs) are small noncoding RNAs, and their best-understood function is to target the methyltransferase fibrillarin to rRNA (for example, SNORD27 performs 2'-O-methylation of A27 in 18S rRNA). Unexpectedly, we found a subset of SNORDs, including SNORD27, in soluble nuclear extract made under native conditions, where fibrillarin was not detected, indicating that a fraction of the SNORD27 RNA likely forms a protein complex different from canonical snoRNAs found in the insoluble nuclear fraction. As part of this previously unidentified complex,SNORD27 regulates the alternative splicing of the transcription factor E2F7p re-mRNA through direct RNA-RNA interaction without methylating the RNA, likely by competing with U1 small nuclear ribonucleoprotein (snRNP). Furthermore, knockdown of SNORD27 activates previously "silent" exons in several other genes through base complementarity across the entire SNORD27 sequence, not just the antisense boxes. Thus, some SNORDs likely function in both rRNA and pre-mRNA processing, which increases the repertoire of splicing regulators and links both processes.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536;
authors.forename: Marina
authors.initials: M
authors.lastname: Falaleeva
authors.affiliation: Department of Experimental and Health Sciences, Universitat Pompeu Fabra, E08003 Barcelona, Spain;
authors.forename: Amadis
authors.initials: A
authors.lastname: Pages
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536;
authors.forename: Zaneta
authors.initials: Z
authors.lastname: Matuszek
authors.affiliation: Department of Genetics, Hebrew University of Jerusalem, 91904 Jerusalem, Israel;
authors.forename: Sana
authors.initials: S
authors.lastname: Hidmi
authors.affiliation: Department of Genetics, Hebrew University of Jerusalem, 91904 Jerusalem, Israel;
authors.forename: Lily
authors.initials: L
authors.lastname: Agranat-Tamir
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536;
authors.forename: Konstantin
authors.initials: K
authors.lastname: Korotkov
authors.affiliation: Department of Microbiology and Molecular Genetics, Computation Center at the Hebrew University and Hadassah Medical Center, 91904 Jerusalem, Israel;
authors.forename: Yuval
authors.initials: Y
authors.lastname: Nevo
authors.affiliation: Department of Experimental and Health Sciences, Universitat Pompeu Fabra, E08003 Barcelona, Spain; Catalan Institution for Research and Advanced Studies, E08010 Barcelona, Spain.
authors.forename: Eduardo
authors.identifier: http://orcid.org/0000-0003-0793-6218
authors.initials: E
authors.lastname: Eyras
authors.affiliation: Department of Genetics, Hebrew University of Jerusalem, 91904 Jerusalem, Israel;
authors.forename: Ruth
authors.initials: R
authors.lastname: Sperling
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536; stefan@stamms-lab.net.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
mesh_terms: D017398:Alternative Splicing; D020029:Base Pairing; D001483:Base Sequence; D002453:Cell Cycle; D002455:Cell Division; D002458:Cell Fractionation / Q000379:methods; D002467:Cell Nucleus / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D050702:E2F7 Transcription Factor / Q000235:genetics; D005091:Exons / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics; D001678:Organelle Biogenesis; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012335:RNA, Ribosomal / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000502:physiology*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012995:Solubility; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D050702:E2F7 Transcription Factor; C481054:E2F7 protein, human; D016376:Oligonucleotides, Antisense; D012322:RNA Precursors; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; D017412:Ribonucleoprotein, U1 Small Nuclear; C047458:fibrillarin
keywords: alternative splicing; gene regulation; pre-mRNA processing; snoRNAs