Trans-splicing and polyadenylation of let-7 microRNA primary transcripts

被引:127
作者
Bracht, J [1 ]
Hunter, S [1 ]
Eachus, R [1 ]
Weeks, P [1 ]
Pasquinelli, AE [1 ]
机构
[1] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
关键词
microRNAs; let-7; trans-splicing; polyadenylation; miRNAs;
D O I
10.1261/rna.7122604
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
Members of the microRNA (miRNA) class of 22-nucleotide RNAs regulate the expression of target genes that contain sequences of antisense complementarity. Maturation of miRNAs involves cleavage of longer primary transcripts, but little is yet understood about how miRNA genes are transcribed and enter the processing pathway. We find that relatively long, polyadenylated transcripts encoded by the Caenorhabditis elegans let-7 gene undergo trans-splicing to the spliced leader 1 (SL1) RNA. Deletions, including removal of the trans-splice site, upstream of mature let-7 sequence result in stable accumulation of primary transcripts and compromised production of mature let-7 RNA in vivo. Our data show that multiple steps of let-7 miRNA biogenesis can be uncoupled, allowing for complex regulation in the production of a functional miRNA. Finally, the observation that let-7 primary transcripts undergo splicing highlights the importance of identifying the sequence of endogenous pri-miRNA substrates recognized by the cellular processing machinery.
引用
收藏
页码:1586 / 1594
页数:9
相关论文
共 45 条
  • [1] MicroRNA pathways in flies and worms: Growth, death, fat, stress, and timing
    Ambros, V
    [J]. CELL, 2003, 113 (06) : 673 - 676
  • [2] MicroRNAs and other tiny endogenous RNAs in C-elegans
    Ambros, V
    Lee, RC
    Lavanway, A
    Williams, PT
    Jewell, D
    [J]. CURRENT BIOLOGY, 2003, 13 (10) : 807 - 818
  • [3] The small RNA profile during Drosophila melanogaster development
    Aravin, AA
    Lagos-Quintana, M
    Yalcin, A
    Zavolan, M
    Marks, D
    Snyder, B
    Gaasterland, T
    Meyer, J
    Tuschl, T
    [J]. DEVELOPMENTAL CELL, 2003, 5 (02) : 337 - 350
  • [4] Regulation of flowering time and floral organ identity by a microRNA and its APETALA2-like target genes
    Aukerman, MJ
    Sakai, H
    [J]. PLANT CELL, 2003, 15 (11) : 2730 - 2741
  • [5] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004)
    Bartel, David P.
    [J]. CELL, 2007, 131 (04) : 11 - 29
  • [6] Human let-7 stem-loop precursors harbor features of RNase III cleavage products
    Basyuk, E
    Suavet, F
    Doglio, A
    Bordonné, R
    Bertrand, E
    [J]. NUCLEIC ACIDS RESEARCH, 2003, 31 (22) : 6593 - 6597
  • [7] TRANSSPLICING AND POLYCISTRONIC TRANSCRIPTION IN CAENORHABDITIS-ELEGANS
    BLUMENTHAL, T
    [J]. TRENDS IN GENETICS, 1995, 11 (04) : 132 - 136
  • [8] Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs
    Bohnsack, MT
    Czaplinski, K
    Görlich, D
    [J]. RNA, 2004, 10 (02) : 185 - 191
  • [9] Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain
    Cerutti, L
    Mian, N
    Bateman, A
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 2000, 25 (10) : 481 - 482
  • [10] MicroRNAs modulate hematopoietic lineage differentiation
    Chen, CZ
    Li, L
    Lodish, HF
    Bartel, DP
    [J]. SCIENCE, 2004, 303 (5654) : 83 - 86