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Sub1/PC4, more than a RNAPII transcription factor

AuthorsGaravís, Miguel; González-Polo, Noelia; Allepuz-Fuster, Paula; Alegrio Louro, Jaime; Fernández-Tornero, Carlos ; Calvo, Olga
Issue Date19-Jul-2017
CitationII Reunión de la Red de Excelencia Temática (2017)
AbstractBiogenesis of mRNA is critically influenced by the phosphorylation state of the carboxy-terminal domain (CTD) in the largest RNA polymerase II (RNAPII) subunit. Several kinases and phosphatases are required to maintain proper CTD phosphorylation levels and, additionally, several other proteins modulate them, including Rpb4/7 and Sub1. The Rpb4/7 heterodimer, constituting the RNAPII stalk, promote phosphatase functions, and Sub1 globally influences CTD phosphorylation, though its mechanism remained mostly unknown until recently. Sub1 was initially identified as a coactivator factor, with a role during transcription initiation, due to conserved functional and structural features with human PC4. However, over the last years many evidences showed that it influences processes downstream during mRNA biogenesis, such as elongation, termination and RNAPII phosphorylation. The recent discover that Sub1 directly interacts with the RNAPII stalk adds new insights into how it achieves all these tasks. Moreover, we showed that this interaction likely occurs via the carboxi-terminal region of Sub1 (Sub1-CT), of unknown function so far. We also demonstrated that a complete RNAPII-CTD is necessary for proper association of Sub1 to chromatin and to the RNAPII. Altogether, our results indicate that Sub1 in association with Rpb4/7 and the CTD phosphatase Fcp1, modulates CTD phosphorylation, which crucially regulates the biogenesis of mRNAs. We also provide evidence indicating that Sub1 contributes to RNAPII clamp function elucidating Sub1 role during the transition from the open to the closed complex formation, thus facilitating transcription elongation. On the other hand, genome wide studies showed that Sub1 also binds to all RNAP III-transcribed genes and the rDNA gene transcribed by RNAPI, though, in this latter case, Sub1 binding is controversial. In agreement, genome wide experiments performed by us show that tRNAs transcription is decreased when lacking SUB1. As in the case of RNAPII, Sub1 works in different steps of RNAPIII transcription cycle. It stimulates both transcription initiation and reinitiation in vitro. Additionally, Sub1 and PC4, as ssDNA binding proteins, have been involved in the maintenance of genome stability. Therefore, it is clear that the role of Sub1 in transcription regulation in particular, and in gene expression in general, is more complicated and important than anticipated. Although many progresses have been done regarding Sub1 role in transcription, several important questions remains unanswered: What is the role of Sub1-CT? Is Sub1 a gene looping factor? Is Sub1 shared by all the three RNAPs?
DescriptionTrabajo presentado en la II Reunión de la Red de Excelencia Temática: RNA Life, celebrada en Madrid (España), los días 19 y 20 de julio de 2017
Appears in Collections:(IQFR) Comunicaciones congresos
(CIB) Comunicaciones congresos
(IBFG) Comunicaciones congresos
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