Your browser doesn't support javascript.
loading
Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip.
Kulkarni, Smita; Ramsuran, Veron; Rucevic, Marijana; Singh, Sukhvinder; Lied, Alexandra; Kulkarni, Viraj; O'hUigin, Colm; Le Gall, Sylvie; Carrington, Mary.
Afiliación
  • Kulkarni S; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139; skulkarni@txbiomed.org.
  • Ramsuran V; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78227.
  • Rucevic M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139.
  • Singh S; Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702.
  • Lied A; KwaZulu-Natal Research Innovation and Sequencing Platform, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
  • Kulkarni V; Centre for the AIDS Programme of Research in South Africa, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa; and.
  • O'hUigin C; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139.
  • Le Gall S; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78227.
  • Carrington M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139.
J Immunol ; 199(11): 3892-3899, 2017 12 01.
Article en En | MEDLINE | ID: mdl-29055006
Genomic variation in the untranslated region (UTR) has been shown to influence HLA class I expression level and associate with disease outcomes. Sequencing of the 3'UTR of common HLA-A alleles indicated the presence of two polyadenylation signals (PAS). The proximal PAS is conserved, whereas the distal PAS is disrupted within certain alleles by sequence variants. Using 3'RACE, we confirmed expression of two distinct forms of the HLA-A 3'UTR based on use of either the proximal or the distal PAS, which differ in length by 100 bp. Specific HLA-A alleles varied in the usage of the proximal versus distal PAS, with some alleles using only the proximal PAS, and others using both the proximal and distal PAS to differing degrees. We show that the short and the long 3'UTR produced similar mRNA expression levels. However, the long 3'UTR conferred lower luciferase activity as compared with the short form, indicating translation inhibition of the long 3'UTR. RNA affinity pull-down followed by mass spectrometry analysis as well as RNA coimmunoprecipitation indicated differential binding of Syncrip to the long versus short 3'UTR. Depletion of Syncrip by small interfering RNA increased surface expression of an HLA-A allotype that uses primarily the long 3'UTR, whereas an allotype expressing only the short form was unaffected. Furthermore, specific blocking of the proximal 3'UTR reduced surface expression without decreasing mRNA expression. These data demonstrate HLA-A allele-specific variation in PAS usage, which modulates their cell surface expression posttranscriptionally.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos HLA-A / Isoformas de Proteínas / Regiones no Traducidas 3' / Sitios de Empalme de ARN / Ribonucleoproteínas Nucleares Heterogéneas / Motivos de Unión al ARN Límite: Humans Idioma: En Revista: J Immunol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos HLA-A / Isoformas de Proteínas / Regiones no Traducidas 3' / Sitios de Empalme de ARN / Ribonucleoproteínas Nucleares Heterogéneas / Motivos de Unión al ARN Límite: Humans Idioma: En Revista: J Immunol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos