Primary microRNA transcripts are processed co-transcriptionally

被引:283
作者
Morlando, Mariangela [1 ,2 ,3 ]
Ballarino, Monica [2 ,3 ]
Gromak, Natalia [1 ]
Pagano, Francesca [2 ,3 ]
Bozzoni, Irene [2 ,3 ]
Proudfoot, Nick J. [1 ]
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[2] Univ Roma La Sapienza, Dept Genet & Mol Biol, Inst Pasteur Cenci Bolognetti, I-00185 Rome, Italy
[3] Univ Roma La Sapienza, IBPM, I-00185 Rome, Italy
基金
英国惠康基金; 英国医学研究理事会;
关键词
D O I
10.1038/nsmb.1475
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
microRNAs (miRNAs) are generated from long primary (pri-) RNA polymerase II (Pol II) -derived transcripts by two RNase III processing reactions: Drosha cleavage of nuclear pri- miRNAs and Dicer cleavage of cytoplasmic pre-miRNAs. Here we show that Drosha cleavage occurs during transcription acting on both independently transcribed and intron-encoded miRNAs. We also show that both 5'-3' and 3'-5' exonucleases associate with the sites where co-transcriptional Drosha cleavage occurs, promoting intron degradation before splicing. We finally demonstrate that miRNAs can also derive from 3' flanking transcripts of Pol II genes. Our results demonstrate that multiple miRNA-containing transcripts are co-transcriptionally cleaved during their synthesis and suggest that exonucleolytic degradation from Drosha cleavage sites in pre-mRNAs may influence the splicing and maturation of numerous mRNAs.
引用
收藏
页码:902 / 909
页数:8
相关论文
共 56 条
[1]   The cotranscriptional assembly of snoRNPs controls the biosynthesis of H/ACA snoRNAs in Saccharomyces cerevisiae [J].
Ballarino, M ;
Morlando, M ;
Pagano, F ;
Fatica, A ;
Bozzoni, I .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (13) :5396-5403
[2]   Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes [J].
Baskerville, S ;
Bartel, DP .
RNA, 2005, 11 (03) :241-247
[3]   Human let-7 stem-loop precursors harbor features of RNase III cleavage products [J].
Basyuk, E ;
Suavet, F ;
Doglio, A ;
Bordonné, R ;
Bertrand, E .
NUCLEIC ACIDS RESEARCH, 2003, 31 (22) :6593-6597
[4]   Discovery of tissue-specific exons using comprehensive human exon microarrays [J].
Clark, Tyson A. ;
Schweitzer, Anthony C. ;
Chen, Tina X. ;
Staples, Michelle K. ;
Lu, Gang ;
Wang, Hui ;
Williams, Alan ;
Blume, John E. .
GENOME BIOLOGY, 2007, 8 (04)
[5]   RNAse III-mediated degradation of unspliced pre-mRNAs and lariat introns [J].
Danin-Kreiselman, M ;
Lee, CY ;
Chanfreau, G .
MOLECULAR CELL, 2003, 11 (05) :1279-1289
[6]   TOP promoter elements control the relative ratio of intron-encoded snoRNA versus spliced mRNA biosynthesis [J].
de Turris, V ;
Di Leva, G ;
Caldarola, S ;
Loreni, F ;
Amaldi, F ;
Bozzoni, I .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 344 (02) :383-394
[7]   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
[8]   Turnover and function of noncoding RNA polymerase II transcripts [J].
Dye, M. J. ;
Gromak, N. ;
Haussecker, D. ;
West, S. ;
Proudfoot, N. J. .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 2006, 71 :275-284
[9]   Exon tethering in transcription by RNA polymerase II [J].
Dye, MJ ;
Gromak, N ;
Proudfoot, NJ .
MOLECULAR CELL, 2006, 21 (06) :849-859
[10]   Multiple transcript cleavage precedes polymerase release in termination by RNA polymerase II [J].
Dye, MJ ;
Proudfoot, NJ .
CELL, 2001, 105 (05) :669-681