Dual Function of C/D Box Small Nucleolar RNAs in RRNA Modification and Alternative Pre-mRNA Splicing

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2016 Mar 10

PMID 26957605

Citations 115

Authors

Marina Falaleeva

Amadis Pages

Zaneta Matuszek

Sana Hidmi

Lily Agranat-Tamir

Konstantin Korotkov

Yuval Nevo

Eduardo Eyras

Ruth Sperling

Stefan Stamm

Affiliations

Soon will be listed here.

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.

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