TRF2: TRansForming the view of general transcription factors

Zehavi, Yonathan; Kedmi, Adi; Ideses, Diana; Juven‐Gershon, Tamar

doi:10.1080/21541264.2015.1004980

Cited by 21 publications

(28 citation statements)

References 84 publications

(134 reference statements)

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“…The phenomenon of convergent transcription is a common occurrence in the human genome, where antisense transcription traverses 30% of human genes, including those genes that harbor CAG, CGG, and GAA repeats and are associated with TNR diseases [23, 39-45]. Antisense transcription may affect gene expression by modulating the efficiency of sense transcription, for instance, by head-on collision between RNAP II complexes; or by recruiting chromatin remodeling factors; or by generating double-stranded RNAs, which may regulate sense transcription [46, 47].…”

Section: Discussionmentioning

confidence: 99%

Mismatch repair enhances convergent transcription-induced cell death at trinucleotide repeats by activating ATR

2016

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Trinucleotide repeat (TNR) expansion beyond a certain threshold results in some 20 incurable neurodegenerative disorders where disease anticipation positively correlates with repeat length. Long TNRs typically display a bias toward further expansion during germinal transmission from parents to offspring, and then are highly unstable in somatic tissues of affected individuals. Understanding mechanisms of TNR instability will provide insights into disease pathogenesis. Previously, we showed that enhanced convergent transcription at long CAG repeat tracks induces TNR instability and cell death via ATR activation. Components of TC-NER (transcription-coupled nucleotide excision repair) and RNaseH enzymes that resolve RNA/DNA hybrids oppose cell death, whereas the MSH2 component of MMR (mismatch repair) enhances cell death. The exact role of the MMR pathway during convergent transcription-induced cell death at CAG repeats is not well understood. In this study, we show that siRNA knockdowns of MMR components—MSH2, MSH3, MLHI, PMS2, and PCNA—reduce DNA toxicity. Furthermore, knockdown of MSH2, MLH1, and PMS2 significantly reduces the frequency of ATR foci formation. These observations suggest that MMR proteins activate DNA toxicity by modulating ATR foci formation during convergent transcription.

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Section: Discussionmentioning

confidence: 99%

Mismatch repair enhances convergent transcription-induced cell death at trinucleotide repeats by activating ATR

2016

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“…TRF3 (TBP2), found only in vertebrates also binds the TATA-element in association with TFIIA and TFIIB to activate transcription19202122. In contrast, TRF2 found in all metazoans, is the most divergent from TBP with only 40% identity in the C-terminal domain812. Like TRF1 and TRF3, TRF2 also binds TFIIA, but it does not selectively recognize the TATA element23242526.…”

mentioning

confidence: 99%

TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression

Martianov

Velt

Davidson

et al. 2016

Sci Rep

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Mammalian genomes encode two genes related to the TATA-box binding protein (TBP), TBP-related factors 2 and 3 (TRF2 and TRF3). Male Trf2−/− mice are sterile and characterized by arrested spermatogenesis at the transition from late haploid spermatids to early elongating spermatids. Despite this characterization, the molecular function of murine Trf2 remains poorly characterized and no direct evidence exists to show that it acts as a bona fide chromatin-bound transcription factor. We show here that Trf2 forms a stable complex with TFIIA or the testis expressed paralogue ALF chaperoned in the cytoplasm by heat shock proteins. We demonstrate for the first time that Trf2 is recruited to active haploid cell promoters together with Tbp, Taf7l and RNA polymerase II. RNA-seq analysis identifies a set of genes activated in haploid spermatids during the first wave of spermatogenesis whose expression is down-regulated by Trf2 inactivation. We therefore propose that Trf2 is recruited to the preinitiation complex as a testis-specific subunit of TFIIA/ALF that cooperates with Tbp and Taf7l to promote haploid cell gene expression.

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“…Finally, we detected copurification of TBP‐related factor 2 (Trf2) with Paip2. Trf2 was located in regions differing from those occupied by TBP . In particular, Trf2 is recruited onto ecdysone‐induced genes as well as is Paip2.…”

Section: Discussionmentioning

confidence: 99%

Paip2 cooperates with Cbp80 at an active promoter and participates in RNA Polymerase II phosphorylation in Drosophila

et al. 2019

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The Paip2 protein is a factor regulating mRNA translation and stability in the cytoplasm. It has also been found in the nuclei of several cell types in Drosophila. Here, we aim to elucidate the functions of Paip2 in the cell nucleus. We find that nuclear Paip2 is a component of an ~300‐kDa protein complex. Paip2 interacts with mRNA capping factor and factors of RNA polymerase II (Pol II) transcription initiation and early elongation. Paip2 functionally cooperates with the Cbp80 subunit of the cap‐binding complex, with both proteins ensuring proper Pol II C‐terminal domain (CTD) Ser5 phosphorylation at the promoter. Thus, Paip2 is a novel player at the stage of mRNA capping and early Pol II elongation.

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TRF2: TRansForming the view of general transcription factors

Cited by 21 publications

References 84 publications

Mismatch repair enhances convergent transcription-induced cell death at trinucleotide repeats by activating ATR

Mismatch repair enhances convergent transcription-induced cell death at trinucleotide repeats by activating ATR

TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression

Paip2 cooperates with Cbp80 at an active promoter and participates in RNA Polymerase II phosphorylation in Drosophila

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