title: A novel myogenic function residing in the 5' non-coding region of Insulin receptor substrate-1 (Irs-1) transcript.
abstract: BACKGROUND
  There is evidence that several messenger RNAs (mRNAs) are bifunctional RNAs, i.e. RNA transcript carrying both protein-coding capacity and activity as functional non-coding RNA via 5' and 3' untranslated regions (UTRs).
  
  
  RESULTS
  In this study, we identified a novel bifunctional RNA that is transcribed from insulin receptor substrate-1 (Irs-1) gene with full-length 5'UTR sequence (FL-Irs-1 mRNA). FL-Irs-1 mRNA was highly expressed only in skeletal muscle tissue. In cultured skeletal muscle C2C12 cells, the FL-Irs-1 transcript functioned as a bifunctional mRNA. The FL-Irs-1 transcript produced IRS-1 protein during differentiation of myoblasts into myotubes; however, this transcript functioned as a regulatory RNA in proliferating myoblasts. The FL-Irs-1 5'UTR contains a partial complementary sequence to Rb mRNA, which is a critical factor for myogenic differentiation. The overexpression of the 5'UTR markedly reduced Rb mRNA expression, and this reduction was fully dependent on the complementary element and was not compensated by IRS-1 protein. Conversely, knockdown of FL-Irs-1 mRNA increased Rb mRNA expression and enhanced myoblast differentiation into myotubes.
  
  
  CONCLUSIONS
  Our findings suggest that the FL-Irs-1 transcript regulates myogenic differentiation as a regulatory RNA in myoblasts.
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. h_nagano1231@yahoo.co.jp.|Facalty of Nutritional Science, Sagami Women's University, Sagamihara, 252-0383, Japan. h_nagano1231@yahoo.co.jp.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. yamagishin@affrc.go.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamagishi
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. c201331003@tokushima-u.ac.jp.
authors.forename: Chisato
authors.initials: C
authors.lastname: Tomida
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. c201102013@tokushima-u.ac.jp.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Yano
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. kt.aibara@mopera.net.
authors.forename: Kana
authors.initials: K
authors.lastname: Aibara
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. kohno@tokushima-u.ac.jp.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. t-abe@tokushima-u.ac.jp.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. ayako-o@nutr.med.tokushima-u.ac.jp.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ohno
authors.affiliation: Graduate school of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki, 852-8521, Japan. hirasaka@nagasaki-u.ac.jp.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirasaka
authors.affiliation: Facalty of Nutritional Science, Sagami Women's University, Sagamihara, 252-0383, Japan. y-okumura@star.sagami-wu.ac.jp.
authors.forename: Yuushi
authors.initials: Y
authors.lastname: Okumura
authors.affiliation: Division of Pharmacology/Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas. ted_mills@mail.utexas.edu.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Mills
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. nikawa@tokushima-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan. kondoshi@nutr.med.tokushima-u.ac.jp.
authors.forename: Shigetada
authors.initials: S
authors.lastname: Teshima-Kondo
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D055504:Insulin Receptor Substrate Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D020121:5' Untranslated Regions; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein