The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression

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. Synopsis The 7SK small nuclear RNP is known to regulate RNA polymerase II elongation via sequestration of P‐TEFb. This work shows that the 7SK snRNP also directly stimulates snRNA transcription by recruiting the little elongation complex. 7SK snRNP interacts with a fraction of RNA polymerase II (RNAPII). 7SK snRNP associates with RNAPII‐specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. 7SK snRNP promotes expression of RNAPII‐specific sn(o)RNAs by forming a larger RNP with the ‘little elongation complex’. 7SK snRNP is a bifunctional RNAPII‐specific transcriptional regulatory factor that controls both mRNA production and sn(o)RNAs synthesis. Graphical Abstract In addition to its role as a negative regulator of transcription elongation by RNA polymerase II, the 7SK snRNP also functions as a canonical transcription factor to positively regulate snRNA transcription.