title: Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle.
abstract: Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.
authors.affiliation: Dept. of Physiology and Biophysics, Univ. of California, Irvine, Irvine, CA 92697, USA. cpandorf@uci.edu
authors.forename: Clay E
authors.initials: CE
authors.lastname: Pandorf
authors.forename: Weihua
authors.initials: W
authors.lastname: Jiang
authors.forename: Anqi X
authors.initials: AX
authors.lastname: Qin
authors.forename: Paul W
authors.initials: PW
authors.lastname: Bodell
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Baldwin
authors.forename: Fadia
authors.initials: F
authors.lastname: Haddad
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics*; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics*; D011441:Propylthiouracil / Q000009:adverse effects; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D016372:RNA, Antisense; D011441:Propylthiouracil; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains