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Diversity of ribosomes at the level of rRNA variation associated with human health and disease.
Rothschild, Daphna; Susanto, Teodorus Theo; Sui, Xin; Spence, Jeffrey P; Rangan, Ramya; Genuth, Naomi R; Sinnott-Armstrong, Nasa; Wang, Xiao; Pritchard, Jonathan K; Barna, Maria.
Afiliación
  • Rothschild D; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Susanto TT; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Sui X; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Spence JP; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Rangan R; Biophysics Program, Stanford University, Stanford, CA 94305, USA.
  • Genuth NR; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
  • Sinnott-Armstrong N; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Wang X; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Pritchard JK; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
  • Barna M; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: mbarna@stanford.edu.
Cell Genom ; 4(9): 100629, 2024 Sep 11.
Article en En | MEDLINE | ID: mdl-39111318
ABSTRACT
With hundreds of copies of rDNA, it is unknown whether they possess sequence variations that form different types of ribosomes. Here, we developed an algorithm for long-read variant calling, termed RGA, which revealed that variations in human rDNA loci are predominantly insertion-deletion (indel) variants. We developed full-length rRNA sequencing (RIBO-RT) and in situ sequencing (SWITCH-seq), which showed that translating ribosomes possess variation in rRNA. Over 1,000 variants are lowly expressed. However, tens of variants are abundant and form distinct rRNA subtypes with different structures near indels as revealed by long-read rRNA structure probing coupled to dimethyl sulfate sequencing. rRNA subtypes show differential expression in endoderm/ectoderm-derived tissues, and in cancer, low-abundance rRNA variants can become highly expressed. Together, this study identifies the diversity of ribosomes at the level of rRNA variants, their chromosomal location, and unique structure as well as the association of ribosome variation with tissue-specific biology and cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribosomas / ARN Ribosómico Límite: Humans Idioma: En Revista: Cell Genom Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribosomas / ARN Ribosómico Límite: Humans Idioma: En Revista: Cell Genom Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos