Many Families of C. elegans MicroRNAs Are Not Essential for Development or Viability

被引:259
作者
Alvarez-Saavedra, Ezequiel [1 ]
Horvitz, H. Robert [1 ]
机构
[1] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA
关键词
CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; RNAS; PROLIFERATION; SPECIFICITY;
D O I
10.1016/j.cub.2009.12.051
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
MicroRNAs (miRNAs) are approximately 23 nt regulatory RNAs that posttranscriptionally inhibit the functions of protein-coding mRNAs. We previously found that most C. elegans miRNAs are individually not essential for development or viability and proposed that paralogous miRNAs might often function redundantly [1]. To test this hypothesis, we generated mutant C. elegans strains that each lack multiple or all members of one of 15 miRNA families. Mutants for 12 of these families did not display strong synthetic abnormalities, suggesting that these miRNA families have subtle roles during development. By contrast, mutants deleted for all members of the mir-35 or mir-51 families died as embryos or early larvae, and mutants deleted for four members of the mir-58 family showed defects in locomotion, body size, and egg laying and an inability to form dauer larvae. Our findings indicate that the regulatory functions of most individual miRNAs and most individual families of miRNAs related in sequence are not critical for development or viability. Conversely, because in some cases miRNA family members act redundantly, our findings emphasize the importance of determining miRNA function in the absence of miRNAs related in sequence.
引用
收藏
页码:367 / 373
页数:7
相关论文
共 34 条
[1]
The let-7 microRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans [J].
Abbott, AL ;
Alvarez-Saavedra, E ;
Miska, EA ;
Lau, NC ;
Bartel, DP ;
Horvitz, HR ;
Ambros, V .
DEVELOPMENTAL CELL, 2005, 9 (03) :403-414
[2]
Differences in vertebrate microRNA expression [J].
Ason, Brandon ;
Darnell, Diana K. ;
Wittbrodt, Beate ;
Berezikov, Eugene ;
Kloosterman, Wigard P. ;
Wittbrodt, Jochen ;
Antin, Parker B. ;
Plasterk, Ronald H. A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (39) :14385-14389
[3]
MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[4]
BARTON MK, 1987, GENETICS, V115, P107
[5]
Principles of MicroRNA-target recognition [J].
Brennecke, J ;
Stark, A ;
Russell, RB ;
Cohen, SM .
PLOS BIOLOGY, 2005, 3 (03) :404-418
[6]
bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila [J].
Brennecke, J ;
Hipfner, DR ;
Stark, A ;
Russell, RB ;
Cohen, SM .
CELL, 2003, 113 (01) :25-36
[7]
BRENNER S, 1974, GENETICS, V77, P71
[8]
DAUERLARVA, A POST-EMBRYONIC DEVELOPMENTAL VARIANT OF NEMATODE CAENORHABDITIS-ELEGANS [J].
CASSADA, RC ;
RUSSELL, RL .
DEVELOPMENTAL BIOLOGY, 1975, 46 (02) :326-342
[9]
Site-directed, Ligase-Independent Mutagenesis (SLIM): a single-tube methodology approaching 100% efficiency in 4 h [J].
Chiu, J ;
March, PE ;
Lee, R ;
Tillett, D .
NUCLEIC ACIDS RESEARCH, 2004, 32 (21) :e174
[10]
Molecular architecture of a miRNA-regulated 3′ UTR [J].
Didiano, Dominic ;
Hobert, Oliver .
RNA, 2008, 14 (07) :1297-1317