PMID- 29450990
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20200225
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 57
IP  - 10
DP  - 2018 Mar 13
TI  - Splicing Site Recognition by Synergy of Three Domains in Splicing Factor RBM10.
PG  - 1563-1567
LID - 10.1021/acs.biochem.7b01242 [doi]
AB  - Splicing factor RBM10 and its close homologues RBM5 and RBM6 govern the splicing 
      of oncogenes such as Fas, NUMB, and Bcl-X. The molecular architecture of these 
      proteins includes zinc fingers (ZnFs) and RNA recognition motifs (RRMs). Three of 
      these domains in RBM10 that constitute the RNA binding part of this splicing 
      factor were found to individually bind RNAs with micromolar affinities. It was 
      thus of interest to further investigate the structural basis of the 
      well-documented high-affinity RNA recognition by RMB10. Here, we investigated RNA 
      binding by combinations of two or three of these domains and discovered that a 
      polypeptide containing RRM1, ZnF1, and RRM2 connected by their natural linkers 
      recognizes a specific sequence of the Fas exon 6 mRNA with an affinity of 20 nM. 
      Nuclear magnetic resonance structures of the RBM10 domains RRM1 and ZnF1 and the 
      natural V354del isoform of RRM2 further confirmed that the interactions with RNA 
      are driven by canonical RNA recognition elements. The well-known high-fidelity 
      RNA splice site recognition by RBM10, and probably by RBM5 and RBM6, can thus be 
      largely rationalized by a cooperative binding action of RRM and ZnF domains.
FAU - Serrano, Pedro
AU  - Serrano P
AD  - Department of Integrative Structural and Computational Biology , The Scripps 
      Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 
      , United States.
FAU - Hammond, John A
AU  - Hammond JA
AD  - Department of Integrative Structural and Computational Biology , The Scripps 
      Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 
      , United States.
FAU - Geralt, Michael
AU  - Geralt M
AD  - Department of Integrative Structural and Computational Biology , The Scripps 
      Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 
      , United States.
FAU - Wuthrich, Kurt
AU  - Wuthrich K
AUID- ORCID: 0000-0003-2612-6616
AD  - Department of Integrative Structural and Computational Biology , The Scripps 
      Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 
      , United States.
AD  - Skaggs Institute for Chemical Biology , The Scripps Research Institute , 10550 
      North Torrey Pines Road , La Jolla , California 92037 , United States.
LA  - eng
GR  - U54 GM094586/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180216
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (RBM10 protein, human)
RN  - 0 (RNA Splice Sites)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - Binding Sites
MH  - Humans
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Protein Conformation
MH  - *RNA Splice Sites
MH  - *RNA Splicing
MH  - RNA-Binding Proteins/chemistry/*metabolism
PMC - PMC6641550
MID - NIHMS1028621
EDAT- 2018/02/17 06:00
MHDA- 2018/05/16 06:00
PMCR- 2019/07/19
CRDT- 2018/02/17 06:00
PHST- 2018/02/17 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2018/02/17 06:00 [entrez]
PHST- 2019/07/19 00:00 [pmc-release]
AID - 10.1021/acs.biochem.7b01242 [doi]
PST - ppublish
SO  - Biochemistry. 2018 Mar 13;57(10):1563-1567. doi: 10.1021/acs.biochem.7b01242. 
      Epub 2018 Feb 16.