Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

Marina Falaleeva; Amadis Pages; Zaneta Matuszek; Sana Hidmi; Lily Agranat-Tamir; Konstantin Korotkov; Yuval Nevo; Eduardo Eyras; Ruth Sperling; Stefan Stamm

doi:10.1073/pnas.1519292113

Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

Marina Falaleeva
, Amadis Pages
, Zaneta Matuszek
, Sana Hidmi
, Lily Agranat-Tamir
, Konstantin Korotkov
, Yuval Nevo
, Eduardo Eyras
, Ruth Sperling
, Stefan Stamm

Research output: Contribution to journal › Article › peer-review

177 Scopus citations

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′-Omethylation 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. alternative splicing, gene regulation, snoRNAs, pre-mRNA processing.

Original language	English
Pages (from-to)	E1625-E1634
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	12
DOIs	https://doi.org/10.1073/pnas.1519292113
State	Published - Mar 22 2016

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS: The authors thank N. J. McGlincy, C. Waechter, K. Collins, and G. Grohs for discussions. We thank the University of Kentucky Proteomics Core, which was supported by National Institute of GeneralMedical Sciences Centers of Biomedical Research Excellence Grant P20GM103486-09 and the Office of the Vice President for Research of the University of Kentucky as well as High-End Instrumentation Grant S10RR029127. This work was supported by Postdoctoral Fellowship 13POST16820024 from the American Heart Association (toM.F.);MINECO (Ministerio de Economía y Competitividad) Spanish Government Grant BIO2014-52566-R (to A.P. and E.E.); Consolider RNAREG Grant CSD2009-00080 (to A.P. and E.E.); Sandra Ibarra Foundation for Cancer Grant FSI2013 (to A.P. and E.E.); AGAUR (Agència de Gestió d'Ajuts Universitaris i de Recerca) Grant 2014-SGR1121 (to A.P. and E.E.); USA-Israel Binational Science Foundation, Transformative Grant 2010508 (to R.S. and S.S.); NIH Grants 01GM079549 (to R.S.) and 01GM083187 (to S.S.); and the Foundation for Prader-Willi Research (S.S.).

Funding

ACKNOWLEDGMENTS: The authors thank N. J. McGlincy, C. Waechter, K. Collins, and G. Grohs for discussions. We thank the University of Kentucky Proteomics Core, which was supported by National Institute of GeneralMedical Sciences Centers of Biomedical Research Excellence Grant P20GM103486-09 and the Office of the Vice President for Research of the University of Kentucky as well as High-End Instrumentation Grant S10RR029127. This work was supported by Postdoctoral Fellowship 13POST16820024 from the American Heart Association (toM.F.);MINECO (Ministerio de Economía y Competitividad) Spanish Government Grant BIO2014-52566-R (to A.P. and E.E.); Consolider RNAREG Grant CSD2009-00080 (to A.P. and E.E.); Sandra Ibarra Foundation for Cancer Grant FSI2013 (to A.P. and E.E.); AGAUR (Agència de Gestió d'Ajuts Universitaris i de Recerca) Grant 2014-SGR1121 (to A.P. and E.E.); USA-Israel Binational Science Foundation, Transformative Grant 2010508 (to R.S. and S.S.); NIH Grants 01GM079549 (to R.S.) and 01GM083187 (to S.S.); and the Foundation for Prader-Willi Research (S.S.).

Funders	Funder number
National Institute of GeneralMedical Sciences Centers of Biomedical Research Excellence	P20GM103486-09
Office of the Vice President for Research at the University of Kentucky	13POST16820024, S10RR029127
Sandra Ibarra Foundation for Cancer	FSI2013
University of Kentucky Proteomics Core
National Institutes of Health (NIH)	01GM083187
National Institute of General Medical Sciences	R01GM079549
American Heart Association
Foundation for Prader Willi Research
United States-Israel Binational Science Foundation	2010508
Agència de Gestió d'Ajuts Universitaris i de Recerca	2014-SGR1121
Ministerio de Economía y Competitividad	BIO2014-52566-R, CSD2009-00080

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1519292113

Cite this

Falaleeva, M., Pages, A., Matuszek, Z., Hidmi, S., Agranat-Tamir, L., Korotkov, K., Nevo, Y., Eyras, E., Sperling, R., & Stamm, S. (2016). Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing. Proceedings of the National Academy of Sciences of the United States of America, 113(12), E1625-E1634. https://doi.org/10.1073/pnas.1519292113

@article{6fc4b514d0824484b63ec73fc40c517d,

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′-Omethylation 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. alternative splicing, gene regulation, snoRNAs, pre-mRNA processing.",

author = "Marina Falaleeva and Amadis Pages and Zaneta Matuszek and Sana Hidmi and Lily Agranat-Tamir and Konstantin Korotkov and Yuval Nevo and Eduardo Eyras and Ruth Sperling and Stefan Stamm",

note = "Funding Information: ACKNOWLEDGMENTS: The authors thank N. J. McGlincy, C. Waechter, K. Collins, and G. Grohs for discussions. We thank the University of Kentucky Proteomics Core, which was supported by National Institute of GeneralMedical Sciences Centers of Biomedical Research Excellence Grant P20GM103486-09 and the Office of the Vice President for Research of the University of Kentucky as well as High-End Instrumentation Grant S10RR029127. This work was supported by Postdoctoral Fellowship 13POST16820024 from the American Heart Association (toM.F.);MINECO (Ministerio de Econom{\'i}a y Competitividad) Spanish Government Grant BIO2014-52566-R (to A.P. and E.E.); Consolider RNAREG Grant CSD2009-00080 (to A.P. and E.E.); Sandra Ibarra Foundation for Cancer Grant FSI2013 (to A.P. and E.E.); AGAUR (Ag{\`e}ncia de Gesti{\'o} d'Ajuts Universitaris i de Recerca) Grant 2014-SGR1121 (to A.P. and E.E.); USA-Israel Binational Science Foundation, Transformative Grant 2010508 (to R.S. and S.S.); NIH Grants 01GM079549 (to R.S.) and 01GM083187 (to S.S.); and the Foundation for Prader-Willi Research (S.S.).",

year = "2016",

month = mar,

day = "22",

doi = "10.1073/pnas.1519292113",

language = "English",

volume = "113",

pages = "E1625--E1634",

number = "12",

}

Falaleeva, M, Pages, A, Matuszek, Z, Hidmi, S, Agranat-Tamir, L, Korotkov, K, Nevo, Y, Eyras, E, Sperling, R & Stamm, S 2016, 'Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 12, pp. E1625-E1634. https://doi.org/10.1073/pnas.1519292113

TY - JOUR

T1 - Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

AU - Falaleeva, Marina

AU - Pages, Amadis

AU - Matuszek, Zaneta

AU - Hidmi, Sana

AU - Agranat-Tamir, Lily

AU - Korotkov, Konstantin

AU - Nevo, Yuval

AU - Eyras, Eduardo

AU - Sperling, Ruth

AU - Stamm, Stefan

N1 - Funding Information: ACKNOWLEDGMENTS: The authors thank N. J. McGlincy, C. Waechter, K. Collins, and G. Grohs for discussions. We thank the University of Kentucky Proteomics Core, which was supported by National Institute of GeneralMedical Sciences Centers of Biomedical Research Excellence Grant P20GM103486-09 and the Office of the Vice President for Research of the University of Kentucky as well as High-End Instrumentation Grant S10RR029127. This work was supported by Postdoctoral Fellowship 13POST16820024 from the American Heart Association (toM.F.);MINECO (Ministerio de Economía y Competitividad) Spanish Government Grant BIO2014-52566-R (to A.P. and E.E.); Consolider RNAREG Grant CSD2009-00080 (to A.P. and E.E.); Sandra Ibarra Foundation for Cancer Grant FSI2013 (to A.P. and E.E.); AGAUR (Agència de Gestió d'Ajuts Universitaris i de Recerca) Grant 2014-SGR1121 (to A.P. and E.E.); USA-Israel Binational Science Foundation, Transformative Grant 2010508 (to R.S. and S.S.); NIH Grants 01GM079549 (to R.S.) and 01GM083187 (to S.S.); and the Foundation for Prader-Willi Research (S.S.).

PY - 2016/3/22

Y1 - 2016/3/22

N2 - 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′-Omethylation 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. alternative splicing, gene regulation, snoRNAs, pre-mRNA processing.

AB - 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′-Omethylation 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. alternative splicing, gene regulation, snoRNAs, pre-mRNA processing.

UR - https://www.scopus.com/pages/publications/84962224958

UR - https://www.scopus.com/pages/publications/84962224958#tab=citedBy

U2 - 10.1073/pnas.1519292113

DO - 10.1073/pnas.1519292113

M3 - Article

C2 - 26957605

AN - SCOPUS:84962224958

SN - 0027-8424

VL - 113

SP - E1625-E1634

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 12

ER -

Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this