title: Multiple distinct small RNAs originate from the same microRNA precursors.
abstract: BACKGROUND
  MicroRNAs (miRNAs), which originate from precursor transcripts with stem-loop structures, are essential gene expression regulators in eukaryotes.
  
  
  RESULTS
  We report 19 miRNA precursors in Arabidopsis that can yield multiple distinct miRNA-like RNAs in addition to miRNAs and miRNA*s. These miRNA precursor-derived miRNA-like RNAs are often arranged in phase and form duplexes with an approximately two-nucleotide 3'-end overhang. Their production depends on the same biogenesis pathway as their sibling miRNAs and does not require RNA-dependent RNA polymerases or RNA polymerase IV. These miRNA-like RNAs are methylated, and many of them are associated with Argonaute proteins. Some of the miRNA-like RNAs are differentially expressed in response to bacterial challenges, and some are more abundant than the cognate miRNAs. Computational and expression analyses demonstrate that some of these miRNA-like RNAs are potentially functional and they target protein-coding genes for silencing. The function of some of these miRNA-like RNAs was further supported by their target cleavage products from the published small RNA degradome data. Our systematic examination of public small-RNA deep sequencing data from four additional plant species (Oryza sativa, Physcomitrella patens, Medicago truncatula and Populus trichocarpa) and four animals (Homo sapiens, Mus musculus, Caenorhabditis elegans and Drosophila) shows that such miRNA-like RNAs exist broadly in eukaryotes.
  
  
  CONCLUSIONS
  We demonstrate that multiple miRNAs could derive from miRNA precursors by sequential processing of Dicer or Dicer-like proteins. Our results suggest that the pool of miRNAs is larger than was previously recognized, and miRNA-mediated gene regulation may be broader and more complex than previously thought.
authors.affiliation: Department of Computer Science and Engineering, Washington University in Saint Louis, Campus Box 1045, Saint Louis, MO 63130, USA. weixiong.zhang@wustl.edu
authors.forename: Weixiong
authors.initials: W
authors.lastname: Zhang
authors.forename: Shang
authors.initials: S
authors.lastname: Gao
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Chellappan
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.forename: Hailing
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D001483:Base Sequence; D005786:Gene Expression Regulation; D006801:Humans; D006868:Hydrolysis; D035683:MicroRNAs / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism*; D018749:RNA, Plant
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D018749:RNA, Plant