Unknown,Transcriptomics,Genomics,Proteomics

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THOC5 controls 3M-BM-4end-processing of immediate early genes via interaction with CPSF100


ABSTRACT: Transcription of immediate early genes (IEGs) in response to extrinsic and intrinsic signals is tightly regulated at multiple stages. THOC5, a member of the TREX (transcription/export) complex plays a role in expression of only a subset of constitutively active genes. In this report, we show that THOC5 plays a role in the 3M-BM-4end-processing of more than 90% of IEGs induced by serum stimulation, however THOC5 depletion does not influence the expression of the most rapidly induced IEGs, such as Fos or Jun. One group of THOC5 target genes, including Id1, Id3 and Wnt11 transcripts were not released from chromatin in THOC5 depleted cells. Another group of genes, such as Myc, and Smad7 transcripts, were released with shortening of 3M-BM-4UTR by alternative cleavage, and were spliced but were exported to a lesser extent in THOC5 depleted cells. Furthermore, upon stimulation with serum THOC5 forms a complex with polyadenylation specific factor 100 (CPSF100). THOC5 is required for recruitment of CPSF100 to 3M-BM-4UTR of THOC5 target genes, but not for THOC5 independent genes. These data suggest the presence of a novel mechanism for the control of immediate early genes response via 3M-BM-4end-processing. In 2 dual-color microarray hybridizations, mRNA expression changes after 1h of FCS treatment were examined. MEF(Rosa26ERT2 Cre: THOC5 (flox/flox)) cells in which a THOC5 knockdown is inducible upon Tamoxifen treatment were analyzed. M4040 represents cells without Taxoxifen pre-treatment (wildtype reference) whereas M4041 represents the same celltype pre-treated for 2 days with Tamoxifen to induce a THOC5 knockdown.

ORGANISM(S): Mus musculus

SUBMITTER: Oliver Dittrich-Breiholz 

PROVIDER: E-GEOD-59561 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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THOC5 controls 3'end-processing of immediate early genes via interaction with polyadenylation specific factor 100 (CPSF100).

Tran Doan Duy Hai DD   Saran Shashank S   Williamson Andrew J K AJ   Pierce Andrew A   Dittrich-Breiholz Oliver O   Wiehlmann Lutz L   Koch Alexandra A   Whetton Anthony D AD   Tamura Teruko T  

Nucleic acids research 20141001 19


Transcription of immediate early genes (IEGs) in response to extrinsic and intrinsic signals is tightly regulated at multiple stages. It is known that untranslated regions of the RNA can play a role in these processes. Here we show that THOC5, a member of the TREX (transcription/export) complex, plays a role in expression of only a subset of constitutively active genes, however transcriptome analysis reveals that more than 90% of IEG were not induced by serum in THOC5 depleted cells. Furthermore  ...[more]

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