Enzymes
UniProtKB help_outline | 4 proteins |
Reaction participants Show >> << Hide
-
Namehelp_outline
a ribonucleotide in U6 snRNA
Identifier
RHEA-COMP:16262
Reactive part
help_outline
- Name help_outline ribonucleotide residue Identifier CHEBI:90675 Charge -1 Formula C5H7O6PR SMILEShelp_outline *[C@@H]1O[C@H](COP(=O)(*)[O-])[C@@H](O*)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 225 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline S-adenosyl-L-methionine Identifier CHEBI:59789 Charge 1 Formula C15H23N6O5S InChIKeyhelp_outline MEFKEPWMEQBLKI-AIRLBKTGSA-O SMILEShelp_outline C[S+](CC[C@H]([NH3+])C([O-])=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 842 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
-
Namehelp_outline
a 2'-O-methylribonucleotide in U6 snRNA
Identifier
RHEA-COMP:16263
Reactive part
help_outline
- Name help_outline 2'-O-methylribonucleotide residue Identifier CHEBI:90676 Charge -1 Formula C6H9O6PR SMILEShelp_outline *[C@@H]1O[C@H](COP(=O)(*)[O-])[C@@H](O*)[C@H]1OC 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline S-adenosyl-L-homocysteine Identifier CHEBI:57856 Charge 0 Formula C14H20N6O5S InChIKeyhelp_outline ZJUKTBDSGOFHSH-WFMPWKQPSA-N SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](CSCC[C@H]([NH3+])C([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 768 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:63088 | RHEA:63089 | RHEA:63090 | RHEA:63091 | |
---|---|---|---|---|
Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
|
Publications
-
LARP7-mediated U6 snRNA modification ensures splicing fidelity and spermatogenesis in mice.
Wang X., Li Z.T., Yan Y., Lin P., Tang W., Hasler D., Meduri R., Li Y., Hua M.M., Qi H.T., Lin D.H., Shi H.J., Hui J., Li J., Li D., Yang J.H., Lin J., Meister G., Fischer U., Liu M.F.
U6 snRNA, as an essential component of the catalytic core of the pre-mRNA processing spliceosome, is heavily modified post-transcriptionally, with 2'-O-methylation being most common. The role of these modifications in pre-mRNA splicing as well as their physiological function in mammals have remain ... >> More
U6 snRNA, as an essential component of the catalytic core of the pre-mRNA processing spliceosome, is heavily modified post-transcriptionally, with 2'-O-methylation being most common. The role of these modifications in pre-mRNA splicing as well as their physiological function in mammals have remained largely unclear. Here we report that the La-related protein LARP7 functions as a critical cofactor for 2'-O-methylation of U6 in mouse male germ cells. Mechanistically, LARP7 promotes U6 loading onto box C/D snoRNP, facilitating U6 2'-O-methylation by box C/D snoRNP. Importantly, ablation of LARP7 in the male germline causes defective U6 2'-O-methylation, massive alterations in pre-mRNA splicing, and spermatogenic failure in mice, which can be rescued by ectopic expression of wild-type LARP7 but not an U6-loading-deficient mutant LARP7. Our data uncover a novel role of LARP7 in regulating U6 2'-O-methylation and demonstrate the functional requirement of such modification for splicing fidelity and spermatogenesis in mice. << Less
-
The Alazami syndrome-associated protein LARP7 guides U6 small nuclear RNA modification and contributes to splicing robustness.
Hasler D., Meduri R., Bak M., Lehmann G., Heizinger L., Wang X., Li Z.T., Sement F.M., Bruckmann A., Dock-Bregeon A.C., Merkl R., Kalb R., Grauer E., Kunstmann E., Zavolan M., Liu M.F., Fischer U., Meister G.
The La-related protein 7 (LARP7) forms a complex with the nuclear 7SK RNA to regulate RNA polymerase II transcription. It has been implicated in cancer and the Alazami syndrome, a severe developmental disorder. Here, we report a so far unknown role of this protein in RNA modification. We show that ... >> More
The La-related protein 7 (LARP7) forms a complex with the nuclear 7SK RNA to regulate RNA polymerase II transcription. It has been implicated in cancer and the Alazami syndrome, a severe developmental disorder. Here, we report a so far unknown role of this protein in RNA modification. We show that LARP7 physically connects the spliceosomal U6 small nuclear RNA (snRNA) with a distinct subset of box C/D small nucleolar RNAs (snoRNAs) guiding U6 2'-O-methylation. Consistently, these modifications are severely compromised in the absence of LARP7. Although general splicing remains largely unaffected, transcriptome-wide analysis revealed perturbations in alternative splicing in LARP7-depleted cells. Importantly, we identified defects in 2'-O-methylation of the U6 snRNA in Alazami syndrome siblings carrying a LARP7 mutation. Our data identify LARP7 as a bridging factor for snoRNA-guided modification of the U6 snRNA and suggest that alterations in splicing fidelity contribute to the etiology of the Alazami syndrome. << Less