Structural highlights
Function
[SNRPA_HUMAN] Binds stem loop II of U1 snRNA. It is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. Binds preferentially to the 5'-UGCAC-3' motif in vitro.[1]
Publication Abstract from PubMed
Cyclic dinucleotides are second messengers that target the adaptor STING and stimulate the innate immune response in mammals. Besides protein receptors, there are bacterial riboswitches that selectively recognize cyclic dinucleotides. We recently discovered a natural riboswitch that targets 3',3'-cGAMP, which is distinguished from the endogenous mammalian signal 2',3'-cGAMP by its backbone connectivity. Here, we report on structures of the aptamer domain of the 3',3'-cGAMP riboswitch from Geobacter in the 3',3'-cGAMP and c-di-GMP bound states. The riboswitch adopts a tuning fork-like architecture with a junctional ligand-binding pocket and different orientations of the arms are correlated with the identity of the bound cyclic dinucleotide. Subsequent biochemical experiments revealed that specificity of ligand recognition can be affected by point mutations outside of the binding pocket, which has implications for both the assignment and reengineering of riboswitches in this structural class.
Structural Basis for Molecular Discrimination by a 3',3'-cGAMP Sensing Riboswitch.,Ren A, Wang XC, Kellenberger CA, Rajashankar KR, Jones RA, Hammond MC, Patel DJ Cell Rep. 2015 Apr 7;11(1):1-12. doi: 10.1016/j.celrep.2015.03.004. Epub 2015 Mar, 26. PMID:25818298[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lutz CS, Cooke C, O'Connor JP, Kobayashi R, Alwine JC. The snRNP-free U1A (SF-A) complex(es): identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factor. RNA. 1998 Dec;4(12):1493-9. PMID:9848648
- ↑ Ren A, Wang XC, Kellenberger CA, Rajashankar KR, Jones RA, Hammond MC, Patel DJ. Structural Basis for Molecular Discrimination by a 3',3'-cGAMP Sensing Riboswitch. Cell Rep. 2015 Apr 7;11(1):1-12. doi: 10.1016/j.celrep.2015.03.004. Epub 2015 Mar, 26. PMID:25818298 doi:http://dx.doi.org/10.1016/j.celrep.2015.03.004
