title: Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain.
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.
authors.affiliation: 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.
authors.forename: King-Hwa
authors.initials: KH
authors.lastname: Ling
authors.affiliation: 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.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brautigan
authors.affiliation: 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.
authors.forename: Sarah
authors.initials: S
authors.lastname: Moore
authors.affiliation: 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.
authors.forename: Rachel
authors.initials: R
authors.lastname: Fraser
authors.affiliation: 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.
authors.forename: Pike-See
authors.initials: PS
authors.lastname: Cheah
authors.affiliation: eResearchSA, University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Raison
authors.affiliation: 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.
authors.forename: Milena
authors.initials: M
authors.lastname: Babic
authors.affiliation: 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.
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Tasman
authors.initials: T
authors.lastname: Daish
authors.affiliation: Theme of Laboratory and Community Genetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia.
authors.forename: Deidre M
authors.initials: DM
authors.lastname: Mattiske
authors.affiliation: Biomedicine Discovery Institute, Monash University, VIC 3800, Australia.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Mann
authors.affiliation: School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Adelson
authors.affiliation: School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Paul Q
authors.initials: PQ
authors.lastname: Thomas
authors.affiliation: 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.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Hahn
authors.affiliation: 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.
authors.forename: Hamish S
authors.initials: HS
authors.lastname: Scott
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D041681:NIH 3T3 Cells; D055495:Neurogenesis; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D016372:RNA, Antisense; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Antisense RNA; Endo-siRNAs; Mouse brain development; Natural antisense transcripts; Noncoding RNA; Small regulatory RNA; piRNAs