Interaction of 7SK with the Smn complex modulates snRNP production

Changhe Ji, Jakob Bader, Pradhipa Ramanathan, Luisa Hennlein, Felix Meissner, Sibylle Jablonka, Matthias Mann, Utz Fischer, Michael Sendtner () and Michael Briese ()
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Changhe Ji: University Hospital Wuerzburg
Jakob Bader: Max Planck Institute of Biochemistry
Pradhipa Ramanathan: University of Wuerzburg
Luisa Hennlein: University Hospital Wuerzburg
Felix Meissner: Max Planck Institute of Biochemistry
Sibylle Jablonka: University Hospital Wuerzburg
Matthias Mann: Max Planck Institute of Biochemistry
Utz Fischer: University of Wuerzburg
Michael Sendtner: University Hospital Wuerzburg
Michael Briese: University Hospital Wuerzburg

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Gene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.

Date: 2021
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DOI: 10.1038/s41467-021-21529-1

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