TY  - JOUR
A1  - Ji, Changhe
A1  - Bader, Jakob
A1  - Ramanathan, Pradhipa
A1  - Hennlein, Luisa
A1  - Meissner, Felix
A1  - Jablonka, Sibylle
A1  - Mann, Matthias
A1  - Fischer, Utz
A1  - Sendtner, Michael
A1  - Briese, Michael
T1  - Interaction of 7SK with the Smn complex modulates snRNP production
JF  - Nature Communications
N2  - 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.
KW  - Molecular neuroscience
KW  - RNA
KW  - RNA splicing
KW  - Transcription
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259125
VL  - 12
IS  - 1
ER  - 
TY  - JOUR
A1  - Scheib, Ulrike
A1  - Broser, Matthias
A1  - Constantin, Oana M.
A1  - Yang, Shang
A1  - Gao, Shiqiang
A1  - Mukherjee, Shatanik
A1  - Stehfest, Katja
A1  - Nagel, Georg
A1  - Gee, Christine E.
A1  - Hegemann, Peter
T1  - Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain
JF  - Nature Communications
N2  - The cyclic nucleotides cAMP and cGMP are important second messengers that orchestrate fundamental cellular responses. Here, we present the characterization of the rhodopsinguanylyl cyclase from Catenaria anguillulae (CaRhGC), which produces cGMP in response to green light with a light to dark activity ratio > 1000. After light excitation the putative signaling state forms with tau = 31 ms and decays with tau = 570 ms. Mutations (up to 6) within the nucleotide binding site generate rhodopsin-adenylyl cyclases (CaRhACs) of which the double mutated YFP-CaRhAC (E497K/C566D) is the most suitable for rapid cAMP production in neurons. Furthermore, the crystal structure of the ligand-bound AC domain (2.25 angstrom) reveals detailed information about the nucleotide binding mode within this recently discovered class of enzyme rhodopsin. Both YFP-CaRhGC and YFP-CaRhAC are favorable optogenetic tools for non-invasive, cell-selective, and spatio-temporally precise modulation of cAMP/cGMP with light.
KW  - Enzymes
KW  - Molecular biophysics
KW  - Molecular neuroscience
KW  - X-ray crystallography
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228517
VL  - 9
ER  -