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Deep sequencing of small RNAs identifies canonical and non-canonical miRNA and endogenous siRNAs in mammalian somatic tissues

Title: Deep sequencing of small RNAs identifies canonical and non-canonical miRNA and endogenous siRNAs in mammalian somatic tissues
Authors: Castellano, L
Stebbing, J
Item Type: Journal Article
Abstract: MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They are characterized by specific maturation processes defined by canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived from different tissues, developmental stages and cell types, partly characterized by either ablation or mutation of the main proteins belonging to miRNA processor complexes, reveals 66 high-confidence new genomic loci coding for miRNAs that could be processed in a canonical or non-canonical manner. A proportion of the newly discovered miRNAs comprises mirtrons, for which we define a new sub-class. Notably, some of these newly discovered miRNAs are generated from untranslated and open reading frames of coding genes, and we experimentally validate these. We also show that many annotated miRNAs do not present miRNA-like features, as they are neither processed by known processing complexes nor loaded on AGO2; this indicates that the current miRNA miRBase database list should be refined and re-defined. Accordingly, a group of them map on ribosomal RNA molecules, whereas others cannot undergo genuine miRNA biogenesis. Notably, a group of annotated miRNAs are Dgcr8 independent and DICER dependent endogenous small interfering RNAs that derive from a unique hairpin formed from a short interspersed nuclear element.
Issue Date: 15-Jan-2013
Date of Acceptance: 19-Dec-2012
URI: http://hdl.handle.net/10044/1/41020
DOI: http://dx.doi.org/10.1093/nar/gks1474
ISSN: 1362-4962
Publisher: Oxford University Press
Start Page: 3339
End Page: 3351
Journal / Book Title: Nucleic Acids Research
Volume: 41
Issue: 5
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: National Institute for Health Research
Cancer Research UK
Funder's Grant Number: NIHR-RP-011-053
C27532/A14549
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
BIOCHEMISTRY & MOLECULAR BIOLOGY
SMALL INTERFERING RNAS
MICROPROCESSOR COMPLEX
MICRORNA BIOGENESIS
MOUSE OOCYTES
GENES
PATHWAY
DROSHA
TRANSCRIPTS
DROSOPHILA
HUNDREDS
Animals
Base Pairing
Base Sequence
Conserved Sequence
DEAD-box RNA Helicases
Embryonic Stem Cells
Gene Expression
HEK293 Cells
High-Throughput Nucleotide Sequencing
Humans
Mice
Mice, Knockout
MicroRNAs
Molecular Sequence Annotation
Molecular Sequence Data
NIH 3T3 Cells
Nucleic Acid Conformation
Organ Specificity
Proteins
RNA, Small Interfering
RNA-Binding Proteins
Ribonuclease III
Sequence Analysis, RNA
Transcriptome
Developmental Biology
05 Environmental Sciences
06 Biological Sciences
08 Information And Computing Sciences
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer