A human snoRNA with microRNA-like functions.
Small noncoding RNAs function in concert with Argonaute (Ago) proteins to regulate gene expression at the level of transcription, mRNA stability, or translation. Ago proteins bind small RNAs and form the core of silencing complexes. Here, we report the analysis of small RNAs associated with human Ago1 and Ago2 revealed by immunoprecipitation and deep sequencing. Among the reads, we find small RNAs originating from the small nucleolar RNA (snoRNA) ACA45. Moreover, processing of ACA45 requires Dicer activity but is independent of Drosha/DGCR8. Using bioinformatic prediction algorithms and luciferase reporter assays, we uncover the mediator subunit CDC2L6 as one potential mRNA target of ACA45 small RNAs, suggesting a role for ACA45-processing products in posttranscriptional gene silencing. We further identify a number of human snoRNAs with microRNA (miRNA)-like processing signatures. We have, therefore, identified a class of small RNAs in human cells that originate from snoRNAs and can function like miRNAs.
Ender
Christine
C
Center for Integrated Protein Science Munich (CIPSM), Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Krek
Azra
A
Friedländer
Marc R
MR
Beitzinger
Michaela
M
Weinmann
Lasse
L
Chen
Wei
W
Pfeffer
Sébastien
S
Rajewsky
Nikolaus
N
Meister
Gunter
G
D000465:Algorithms; D060565:Argonaute Proteins; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000166:cytology; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III
C115848:AGO1 protein, human; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; D035683:MicroRNAs; D034741:RNA, Small Interfering; D020537:RNA, Small Nucleolar; D034743:RNA-Induced Silencing Complex; D008156:Luciferases; D004722:Endoribonucleases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases