Behind the scenes of a small RNA gene-silencing pathway

被引:17
作者
Ku, Gregory [1 ,2 ]
McManus, Michael T. [1 ,3 ]
机构
[1] Univ Calif San Francisco, UCSF Diabet Ctr, San Francisco, CA 94122 USA
[2] Univ Calif San Francisco, Dept Med, Div Endocrinol & Metab, San Francisco, CA 94122 USA
[3] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94122 USA
关键词
D O I
10.1089/hum.2007.1226
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
RNA interference (RNAi) is a sequence-specific gene-silencing phenomenon mediated by double-stranded RNA. RNAi is made possible through the activity of an evolutionarily conserved RNA-protein machinery that is utilized by microRNAs (miRNAs), endogenously produced 21- to 23-nucleotide noncoding RNAs. As RNA-based therapeutics come of age, understanding the miRNA pathway and the mechanism of posttranscriptional gene silencing is paramount. Studies have pointed to a critical role for miRNAs in human development and disease and revealed an unanticipated complexity in the mechanisms of regulation of gene expression. This review discusses advances in the biogenesis of miRNAs, their modes of action, and implications for RNA- based treatments.
引用
收藏
页码:17 / 26
页数:10
相关论文
共 119 条
[41]   Position-specific chemical modification of siRNAs reduces "off-target'' transcript silencing [J].
Jackson, Aimee L. ;
Burchard, Julja ;
Leake, Devin ;
Reynolds, Angela ;
Schelter, Janell ;
Guo, Jie ;
Johnson, Jason M. ;
Lim, Lee ;
Karpilow, Jon ;
Nichols, Kim ;
Marshall, William ;
Khvorova, Anastasia ;
Linsley, Peter S. .
RNA, 2006, 12 (07) :1197-1205
[42]   Expression profiling reveals off-target gene regulation by RNAi [J].
Jackson, AL ;
Bartz, SR ;
Schelter, J ;
Kobayashi, SV ;
Burchard, J ;
Mao, M ;
Li, B ;
Cavet, G ;
Linsley, PS .
NATURE BIOTECHNOLOGY, 2003, 21 (06) :635-637
[43]   Effective RNAi-mediated gene silencing without interruption of the endogenous microRNA pathway [J].
John, Matthias ;
Constien, Rainer ;
Akinc, Akin ;
Goldberg, Michael ;
Moon, Young-Ah ;
Spranger, Martina ;
Hadwiger, Philipp ;
Soutschek, Juergen ;
Vornlocher, Hans-Peter ;
Manoharan, Muthiah ;
Stoffel, Markus ;
Langer, Robert ;
Anderson, Daniel G. ;
Horton, Jay D. ;
Koteliansky, Victor ;
Bumcrot, David .
NATURE, 2007, 449 (7163) :745-U12
[44]   Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing [J].
Kanellopoulou, C ;
Muljo, SA ;
Kung, AL ;
Ganesan, S ;
Drapkin, R ;
Jenuwein, T ;
Livingston, DM ;
Rajewsky, K .
GENES & DEVELOPMENT, 2005, 19 (04) :489-501
[45]   Characterization of pancreatic transcription factor pdx-1 binding sites using promoter Microarray and serial analysis of chromatin occupancy [J].
Keller, David M. ;
McWeeney, Shannon ;
Arsenlis, Athanasios ;
Drouin, Jacques ;
Wright, Christopher V. E. ;
Wang, Haiyan ;
Wollheim, Claes B. ;
White, Peter ;
Kaestner, Klaus H. ;
Goodman, Richard H. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (44) :32084-32092
[46]   The role of site accessibility in microRNA target recognition [J].
Kertesz, Michael ;
Iovino, Nicola ;
Unnerstall, Ulrich ;
Gaul, Ulrike ;
Segal, Eran .
NATURE GENETICS, 2007, 39 (10) :1278-1284
[47]  
Khvorova A, 2003, CELL, V115, P209, DOI 10.1016/S0092-8674(03)00801-8
[48]   Conversion of pre-RISC to holo-RISC by Ago2 during assembly of RNAi complexes [J].
Kim, Kevin ;
Lee, Young Sik ;
Carthew, Richard W. .
RNA, 2007, 13 (01) :22-29
[49]   Processing of intronic microRNAs [J].
Kim, Young-Kook ;
Kim, V. Narry .
EMBO JOURNAL, 2007, 26 (03) :775-783
[50]   An mRNA m7G cap binding-like motif within human Ago2 represses translation [J].
Kiriakidou, Marianthi ;
Tan, Grace S. ;
Lamprinaki, Styliani ;
De Planell-Saguer, Mariangels ;
Nelson, Peter T. ;
Mourelatos, Zissimos .
CELL, 2007, 129 (06) :1141-1151