PMID- 26641712
OWN - NLM
STAT- MEDLINE
DCOM- 20160513
LR  - 20181113
IS  - 1545-9985 (Electronic)
IS  - 1545-9993 (Print)
IS  - 1545-9985 (Linking)
VI  - 23
IP  - 1
DP  - 2016 Jan
TI  - Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal 
      protein Unkempt.
PG  - 16-23
LID - 10.1038/nsmb.3140 [doi]
AB  - Unkempt is an evolutionarily conserved RNA-binding protein that regulates 
      translation of its target genes and is required for the establishment of the 
      early bipolar neuronal morphology. Here we determined the X-ray crystal structure 
      of mouse Unkempt and show that its six CCCH zinc fingers (ZnFs) form two compact 
      clusters, ZnF1-3 and ZnF4-6, that recognize distinct trinucleotide RNA 
      substrates. Both ZnF clusters adopt a similar overall topology and use distinct 
      recognition principles to target specific RNA sequences. Structure-guided point 
      mutations reduce the RNA binding affinity of Unkempt both in vitro and in vivo, 
      ablate Unkempt's translational control and impair the ability of Unkempt to 
      induce a bipolar cellular morphology. Our study unravels a new mode of RNA 
      sequence recognition by clusters of CCCH ZnFs that is critical for 
      post-transcriptional control of neuronal morphology.
FAU - Murn, Jernej
AU  - Murn J
AD  - Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
AD  - Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, 
      USA.
FAU - Teplova, Marianna
AU  - Teplova M
AD  - Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New 
      York, USA.
FAU - Zarnack, Kathi
AU  - Zarnack K
AD  - Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, 
      Frankfurt am Main, Germany.
FAU - Shi, Yang
AU  - Shi Y
AD  - Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
AD  - Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, 
      USA.
FAU - Patel, Dinshaw J
AU  - Patel DJ
AD  - Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New 
      York, USA.
LA  - eng
SI  - PDB/5ELH
SI  - PDB/5ELK
GR  - R01 GM104962/GM/NIGMS NIH HHS/United States
GR  - P3O CA008748/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - MH096066/MH/NIMH NIH HHS/United States
GR  - R01 MH096066/MH/NIMH NIH HHS/United States
GR  - GM104962/GM/NIGMS NIH HHS/United States
GR  - U54 HD090255/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151207
PL  - United States
TA  - Nat Struct Mol Biol
JT  - Nature structural & molecular biology
JID - 101186374
RN  - 0 (Carrier Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (unkempt protein, mouse)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*chemistry/*metabolism
MH  - Crystallography, X-Ray
MH  - Mice
MH  - Models, Molecular
MH  - *Nucleotide Motifs
MH  - Protein Binding
MH  - Protein Conformation
MH  - RNA/*metabolism
MH  - RNA-Binding Proteins/*metabolism
MH  - *Zinc Fingers
PMC - PMC4703518
MID - NIHMS743624
EDAT- 2015/12/08 06:00
MHDA- 2016/05/14 06:00
PMCR- 2016/01/06
CRDT- 2015/12/08 06:00
PHST- 2015/07/05 00:00 [received]
PHST- 2015/11/12 00:00 [accepted]
PHST- 2015/12/08 06:00 [entrez]
PHST- 2015/12/08 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
PHST- 2016/01/06 00:00 [pmc-release]
AID - 10.1038/nsmb.3140 [doi]
PST - ppublish
SO  - Nat Struct Mol Biol. 2016 Jan;23(1):16-23. doi: 10.1038/nsmb.3140. Epub 2015 Dec 
      7.