title: Mechanisms of genome instability induced by RNA-processing defects.
abstract: The role of normal transcription and RNA processing in maintaining genome integrity is becoming increasingly appreciated in organisms ranging from bacteria to humans. Several mutations in RNA biogenesis factors have been implicated in human cancers, but the mechanisms and potential connections to tumor genome instability are not clear. Here, we discuss how RNA-processing defects could destabilize genomes through mutagenic R-loop structures and by altering expression of genes required for genome stability. A compelling body of evidence now suggests that researchers should be directly testing these mechanisms in models of human cancer.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
authors.forename: Yujia A
authors.initials: YA
authors.lastname: Chan
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z3, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Hieter
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z3, Canada; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, V5Z 1L3, Canada. Electronic address: pstirling@bccrc.ca.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stirling
mesh_terms: D000818:Animals; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D020871:RNA Stability; D059467:Transcriptome
chemical_list: D012313:RNA
keywords: R-loops; RNA processing; cancer; genome instability; transcriptome