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The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, regulates the mRNA elongation capacity of RNA polymerase II (RNAPII) through controlling the nuclear activity of positive transcription elongation factor b (P-TEFb). Here, we demonstrate that the human 7SK snRNP also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII-specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. The 7SK snRNA specifically associates with a fraction of RNAPII hyperphosphorylated at Ser5 and Ser7, which is a hallmark of RNAPII engaged in snRNA synthesis. Chromatin immunoprecipitation (ChIP) and chromatin isolation by RNA purification (ChIRP) experiments revealed enrichments for all components of the 7SK snRNP on RNAPII-specific sn/snoRNA genes. Depletion of 7SK snRNA or Larp7 disrupts LEC integrity, inhibits RNAPII recruitment to RNAPII-specific sn/snoRNA genes, and reduces nascent snRNA and snoRNA synthesis. Thus, through controlling both mRNA elongation and sn/snoRNA synthesis, the 7SK snRNP is a key regulator of nuclear RNA production by RNAPII.

Original publication

DOI

10.15252/embj.201695740

Type

Journal article

Journal

The EMBO Journal

Publication Date

04/2017

Volume

36

Pages

934 - 948

Addresses

Laboratoire de Biologie Moléculaire Eucaryote, Centre de Biologie Intégrative (CBI), CNRS, UPS, Université de Toulouse, Toulouse Cedex 9, France sylvain.egloff@ibcg.biotoul.fr tamas@ibcg.biotoul.fr.

Keywords

Hela Cells, Humans, RNA Polymerase II, Ribonucleoproteins, Transcription Factors, RNA, Small Nuclear, Chromatin Immunoprecipitation, Gene Expression Regulation