DGCR8 HITS-CLIP reveals novel functions for the Microprocessor

被引：170
作者：
Macias, Sara [1 ]
Plass, Mireya [2 ,3 ]
Stajuda, Agata [1 ]
Michlewski, Gracjan [1 ]
Eyras, Eduardo [2 ,4 ]
Caceres, Javier F. [1 ]
机构：
[1] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Med Res Council,Human Genet Unit, Edinburgh, Midlothian, Scotland
[2] Univ Pompeu Fabra, Computat Genom Grp, Barcelona, Spain
[3] Univ Copenhagen, Dept Biol, Bioinformat Ctr, Copenhagen N, Denmark
[4] Catalan Inst Res & Adv Studies, Barcelona, Spain
来源：
NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 08期
基金：
英国医学研究理事会; 英国惠康基金;
关键词：
MICRORNA BIOGENESIS; NUCLEAR EXPORT; WIDE IDENTIFICATION; BINDING PROTEIN; RNA; SITES; RECOGNITION; DROSHA; TRANSCRIPTS; EXPRESSION;
D O I：
10.1038/nsmb.2344
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as the endonuclease. Using high-throughput sequencing and cross-linking immunoprecipitation (HITS-CLIP) we identified RNA targets of DGCR8 in human cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs also comprised several hundred mRNAs as well as small nucleolar RNAs (snoRNAs) and long noncoding RNAs. We found that the Microprocessor controlled the abundance of several mRNAs as well as of MALAT1. By contrast, DGCR8-mediated cleavage of snoRNAs was independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Binding of DGCR8 to cassette exons is a new mechanism for regulation of the relative abundance of alternatively spliced isoforms. These data provide insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs.
引用
收藏
页码：760 / 766
页数：7
相关论文
共 48 条
[1]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[2]   Dicer is essential for mouse development [J].
Bernstein, E ;
Kim, SY ;
Carmell, MA ;
Murchison, EP ;
Alcorn, H ;
Li, MZ ;
Mills, AA ;
Elledge, SJ ;
Anderson, KV ;
Hannon, GJ .
NATURE GENETICS, 2003, 35 (03) :215-217
[3]   Role for a bidentate ribonuclease in the initiation step of RNA interference [J].
Bernstein, E ;
Caudy, AA ;
Hammond, SM ;
Hannon, GJ .
NATURE, 2001, 409 (6818) :363-366
[4]   Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs [J].
Bohnsack, MT ;
Czaplinski, K ;
Görlich, D .
RNA, 2004, 10 (02) :185-191
[5]   Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps [J].
Chi, Sung Wook ;
Zang, Julie B. ;
Mele, Aldo ;
Darnell, Robert B. .
NATURE, 2009, 460 (7254) :479-486
[6]   Canonical and alternate functions of the microRNA biogenesis machinery [J].
Chong, Mark M. W. ;
Zhang, Guoan ;
Cheloufi, Sihem ;
Neubert, Thomas A. ;
Hannon, Gregory J. ;
Littman, Dan R. .
GENES & DEVELOPMENT, 2010, 24 (17) :1951-1960
[7]   Regulation of MicroRNA Biogenesis: A miRiad of mechanisms [J].
Davis, Brandi N. ;
Hata, Akiko .
CELL COMMUNICATION AND SIGNALING, 2009, 7
[8]   Processing of primary microRNAs by the Microprocessor complex [J].
Denli, AM ;
Tops, BBJ ;
Plasterk, RHA ;
Ketting, RF ;
Hannon, GJ .
NATURE, 2004, 432 (7014) :231-235
[9]   A Human snoRNA with MicroRNA-Like Functions [J].
Ender, Christine ;
Krek, Azra ;
Friedlaender, Marc R. ;
Beitzinger, Michaela ;
Weinmann, Lasse ;
Chen, Wei ;
Pfeffer, Sebastien ;
Rajewsky, Nikolaus ;
Meister, Gunter .
MOLECULAR CELL, 2008, 32 (04) :519-528
[10]   DGCR8 recognizes primary transcripts of microRNAs through highly cooperative binding and formation of higher-order structures [J].
Faller, Michael ;
Toso, Daniel ;
Matsunaga, Michio ;
Atanasov, Ivo ;
Senturia, Rachel ;
Chen, Yanqiu ;
Zhou, Z. Hong ;
Guo, Feng .
RNA, 2010, 16 (08) :1570-1583
12345