TY - JOUR
T1 - Dicer partner proteins tune the length of mature miRNAs in flies and mammals
AU - Fukunaga, Ryuya
AU - Han, Bo W.
AU - Hung, Jui Hung
AU - Xu, Jia
AU - Weng, Zhiping
AU - Zamore, Phillip D.
N1 - Funding Information:
We thank Haruhiko and Mikiko Siomi for strains and antibodies; Richard Carthew, Qinghua Liu, and the Bloomington Stock Center for strains; Ganes Sen and Robert Braun for MEF cells; Ian MacRae for human Dicer plasmid; Lin Wang and Lauren Dedow for RNA-Seq library protocols; Chengjian Li for help with small RNA libraries; Wei Wang for bioinformatics help; Alicia Boucher, Cindy Tipping, and Shengmei Ma for fly husbandry; and Traci Hall, Gang Lu, and members of the Zamore laboratory for discussion, advice, and comments on the manuscript. This work was supported in part by the National Institutes of Health (GM62862 and GM65236) and a JSPS Research Fellowship for Research Abroad and a Charles A. King Trust Postdoctoral Fellowship to R.F. P.D.Z. is a member of the scientific advisory board of Regulus Therapeutics.
PY - 2012/10/26
Y1 - 2012/10/26
N2 - Drosophila Dicer-1 produces microRNAs (miRNAs) from pre-miRNA, whereas Dicer-2 generates small interfering RNAs (siRNAs) from long dsRNA. Alternative splicing of the loquacious (loqs) mRNA generates three distinct Dicer partner proteins. To understand the function of each, we constructed flies expressing Loqs-PA, Loqs-PB, or Loqs-PD. Loqs-PD promotes both endo- and exo-siRNA production by Dicer-2. Loqs-PA or Loqs-PB is required for viability, but the proteins are not fully redundant: a specific subset of miRNAs requires Loqs-PB. Surprisingly, Loqs-PB tunes where Dicer-1 cleaves pre-miR-307a, generating a longer miRNA isoform with a distinct seed sequence and target specificity. The longer form of miR-307a represses glycerol kinase and taranis mRNA expression. The mammalian Dicer-partner TRBP, a Loqs-PB homolog, similarly tunes where Dicer cleaves pre-miR-132. Thus, Dicer-binding partner proteins change the choice of cleavage site by Dicer, producing miRNAs with target specificities different from those made by Dicer alone or Dicer bound to alternative protein partners.
AB - Drosophila Dicer-1 produces microRNAs (miRNAs) from pre-miRNA, whereas Dicer-2 generates small interfering RNAs (siRNAs) from long dsRNA. Alternative splicing of the loquacious (loqs) mRNA generates three distinct Dicer partner proteins. To understand the function of each, we constructed flies expressing Loqs-PA, Loqs-PB, or Loqs-PD. Loqs-PD promotes both endo- and exo-siRNA production by Dicer-2. Loqs-PA or Loqs-PB is required for viability, but the proteins are not fully redundant: a specific subset of miRNAs requires Loqs-PB. Surprisingly, Loqs-PB tunes where Dicer-1 cleaves pre-miR-307a, generating a longer miRNA isoform with a distinct seed sequence and target specificity. The longer form of miR-307a represses glycerol kinase and taranis mRNA expression. The mammalian Dicer-partner TRBP, a Loqs-PB homolog, similarly tunes where Dicer cleaves pre-miR-132. Thus, Dicer-binding partner proteins change the choice of cleavage site by Dicer, producing miRNAs with target specificities different from those made by Dicer alone or Dicer bound to alternative protein partners.
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U2 - 10.1016/j.cell.2012.09.027
DO - 10.1016/j.cell.2012.09.027
M3 - Article
C2 - 23063653
AN - SCOPUS:84868106469
SN - 0092-8674
VL - 151
SP - 533
EP - 546
JO - Cell
JF - Cell
IS - 3
ER -