期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 12, 页码 E1625-E1634出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1519292113
关键词
alternative splicing; gene regulation; snoRNAs; pre-mRNA processing
资金
- National Institute of General Medical Sciences Centers of Biomedical Research Excellence [P20GM103486-09]
- Office of the Vice President for Research of the University of Kentucky
- High-End Instrumentation Grant [S10RR029127]
- American Heart Association [13POST16820024]
- MINECO (Ministerio de Economia y Competitividad) Spanish Government Grant [BIO2014-52566-R]
- Consolider RNAREG Grant [CSD2009-00080]
- Sandra Ibarra Foundation for Cancer Grant [FSI2013]
- AGAUR (Agencia de Gestio d'Ajuts Universitaris i de Recerca) Grant [2014-SGR1121]
- USA-Israel Binational Science Foundation [2010508]
- NIH [01GM079549, 01GM083187]
- Foundation for Prader-Willi Research
- ICREA Funding Source: Custom
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 E2F7 pre-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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