Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain

King-Hwa Ling; Peter J Brautigan; Sarah Moore; Rachel Fraser; Pike-See Cheah; Joy M Raison; Milena Babic; Young Kyung Lee; Tasman Daish; Deidre M Mattiske; Jeffrey R Mann; David L Adelson; Paul Q Thomas; Christopher N Hahn; Hamish S Scott

doi:10.1016/j.ygeno.2016.01.006

Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain

Genomics. 2016 Mar;107(2-3):88-99. doi: 10.1016/j.ygeno.2016.01.006. Epub 2016 Jan 21.

Authors

Affiliations

¹ Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, P.O. Box 14 Rundle Mall Post Office, Adelaide, SA 5000, Australia; School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA 5005, Australia; NeuroBiology & Genetics Group, Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor DE, Malaysia. Electronic address: lkh@upm.edu.my.
² Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, P.O. Box 14 Rundle Mall Post Office, Adelaide, SA 5000, Australia.
³ NeuroBiology & Genetics Group, Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor DE, Malaysia; School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia; Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.
⁴ eResearchSA, University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.
⁵ School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
⁶ Theme of Laboratory and Community Genetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia.
⁷ Biomedicine Discovery Institute, Monash University, VIC 3800, Australia.
⁸ Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, P.O. Box 14 Rundle Mall Post Office, Adelaide, SA 5000, Australia; School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: hamish.scott@health.sa.gov.au.

PMID: 26802803
DOI: 10.1016/j.ygeno.2016.01.006

Abstract

Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3.

Keywords: Antisense RNA; Endo-siRNAs; Mouse brain development; Natural antisense transcripts; Noncoding RNA; Small regulatory RNA; piRNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / growth & development*
Brain / metabolism
Cytoplasm / metabolism
DEAD-box RNA Helicases / metabolism
Gene Expression Regulation, Developmental
Mice
NIH 3T3 Cells
Neurogenesis
RNA, Antisense / genetics*
RNA, Antisense / metabolism
RNA, Double-Stranded / genetics
RNA, Double-Stranded / metabolism*
RNA, Small Interfering / metabolism*
Ribonuclease III / metabolism
SOXC Transcription Factors / genetics*
SOXC Transcription Factors / metabolism

Substances

RNA, Antisense
RNA, Double-Stranded
RNA, Small Interfering
SOXC Transcription Factors
Sox4 protein, mouse
Dicer1 protein, mouse
Ribonuclease III
DEAD-box RNA Helicases