PMID- 10556282
OWN - NLM
STAT- MEDLINE
DCOM- 20000124
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 13
DP  - 1999 Dec
TI  - Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly:
      implications for spinal muscular atrophy.
PG  - 2351-7
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disease of spinal motor
      neurons caused by reduced levels of functional survival of motor neurons (SMN)
      protein. SMN is part of a macromolecular complex that contains the
      SMN-interacting protein 1 (SIP1) and spliceosomal Sm proteins. Although it is
      clear that SIP1 as a component of this complex is essential for spliceosomal
      uridine-rich small ribonucleoprotein (U snRNP) assembly, the role of SMN and its 
      functional interactions with SIP1 and Sm proteins are poorly understood. Here we 
      show that the central region of SMN comprising a tudor domain facilitates direct 
      binding to Sm proteins. Strikingly, the SMA-causing missense mutation E134K
      within the tudor domain severely reduced the ability of SMN to interact with Sm
      proteins. Moreover, antibodies directed against the tudor domain prevent Sm
      protein binding to SMN and abolish assembly of U snRNPs in vivo. Thus, our data
      show that SMN is an essential U snRNP assembly factor and establish a direct
      correlation between defects in the biogenesis of U snRNPs and SMA.
FAU - Buhler, D
AU  - Buhler D
AD  - Max-Planck-Institut fur Biochemie, Am Klopferspitz 18a, D-82152 Martinsried,
      Germany,
FAU - Raker, V
AU  - Raker V
FAU - Luhrmann, R
AU  - Luhrmann R
FAU - Fischer, U
AU  - Fischer U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Autoantigens)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (GEMIN2 protein, human)
RN  - 0 (Immune Sera)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Ribonucleoproteins, Small Nuclear)
RN  - 0 (SMN Complex Proteins)
RN  - 0 (snRNP Core Proteins)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
MH  - Animals
MH  - Autoantigens/*metabolism
MH  - Blotting, Western
MH  - Cyclic AMP Response Element-Binding Protein
MH  - Immune Sera
MH  - In Vitro Techniques
MH  - Muscular Atrophy, Spinal/genetics/*metabolism
MH  - Nerve Tissue Proteins/immunology/*metabolism
MH  - Oocytes/metabolism
MH  - Protein Structure, Tertiary
MH  - RNA-Binding Proteins
MH  - Rabbits
MH  - Ribonucleoproteins, Small Nuclear/chemistry/immunology/*metabolism
MH  - SMN Complex Proteins
MH  - Spliceosomes/*metabolism
MH  - Uridine/chemistry
MH  - Xenopus laevis
MH  - snRNP Core Proteins
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
AID - ddc293 [pii]
AID - 10.1093/hmg/8.13.2351 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Dec;8(13):2351-7. doi: 10.1093/hmg/8.13.2351.