Nuclear compartmentalization and dynamics of the poly(A)-binding protein nuclear 1 (PABPN1) inclusions in supraoptic neurons under physiological and osmotic stress conditions.
Nuclear aggregation of the expanded polyalanine tract in the poly(A)-binding protein nuclear 1 (PABPN1) is the pathological hallmark of oculopharyngeal muscular dystrophy. However, wild type PABPN1 aggregates into nuclear inclusion in oxytocin-producing neurons under physiological conditions. In this study we have analyzed the nuclear organization and dynamics of PABPN1 inclusions in oxytocin-producing neurons. We demonstrated that PABPN1 inclusions represent a distinct compartment of the interchromatin region. They establish a spatial relationship with nuclear speckles, Cajal bodies and clastosomes. PABPN1 inclusions accumulate poly(A) RNA, but do not concentrate highly expressed mRNAs in oxytocin producing neurons and the mRNA-binding proteins hnRNP C, Y14 and REF. PABPN1 inclusions are dynamic structures that appear during the postnatal period and their number decrease in response to the activation of transcription. Our results support that the RNA retained in the PABPN1 inclusions is a noncoding regulatory RNA involved in some aspects of nuclear RNA metabolism.
Villagra
Nuria T
NT
Department of Anatomy and Cell Biology, University of Cantabria, Santander, Spain.
Bengoechea
Rocio
R
Vaqué
José P
JP
Llorca
Javier
J
Berciano
Maria T
MT
Lafarga
Miguel
M
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000648:ultrastructure*; D017711:Nonlinear Dynamics; D009687:Nuclear Proteins / Q000378:metabolism; D009997:Osmotic Pressure; D010121:Oxytocin / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism; D013495:Supraoptic Nucleus / Q000166:cytology* / Q000254:growth & development
D006657:Histones; D009687:Nuclear Proteins; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D020718:Ribonucleoproteins, Small Nucleolar; D010121:Oxytocin