Npl3, a new link between RNA-binding proteins and the maintenance of genome integrity.
The mRNA is co-transcriptionally bound by a number of RNA-binding proteins (RBPs) that contribute to its processing and formation of an export-competent messenger ribonucleoprotein particle (mRNP). In the last few years, increasing evidence suggests that RBPs play a key role in preventing transcription-associated genome instability. Part of this instability is mediated by the accumulation of co-transcriptional R loops, which may impair replication fork (RF) progression due to collisions between transcription and replication machineries. In addition, some RBPs have been implicated in DNA repair and/or the DNA damage response (DDR). Recently, the Npl3 protein, one of the most abundant heterogeneous nuclear ribonucleoproteins (hnRNPs) in yeast, has been shown to prevent transcription-associated genome instability and accumulation of RF obstacles, partially associated with R-loop formation. Interestingly, Npl3 seems to have additional functions in DNA repair, and npl3∆ mutants are highly sensitive to genotoxic agents, such as the antitumor drug trabectedin. Here we discuss the role of Npl3 in particular, and RBPs in general, in the connection of transcription with replication and genome instability, and its effect on the DDR.
Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER; Universidad de Sevilla-CSIC; Seville, Spain.
José M
JM
Santos-Pereira
Instituto de Biología Molecular y Celular del Cáncer; Universidad de Salamanca-CSIC; Salamanca, Spain.
Ana B
AB
Herrero
Instituto de Biología Funcional y Genómica; Universidad de Salamanca-CSIC; Salamanca, Spain.
Sergio
S
Moreno
Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER; Universidad de Sevilla-CSIC; Seville, Spain.
Andrés
A
Aguilera
D004260:DNA Repair; D004261:DNA Replication; D004149:Dioxoles / Q000494:pharmacology; D042822:Genomic Instability; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D000077606:Trabectedin; D014158:Transcription, Genetic
D004149:Dioxoles; C077734:NPL3 protein, S cerevisiae; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
DNA damage response; DNA repair; Npl3; R loops; RNA-binding proteins; transcription-associated genome instability; transcription-replication conflicts