The Gemin5 protein of the SMN complex identifies snRNAs.

The survival of motor neurons protein (SMN) is part of a large complex that contains six other proteins, Gemins2-7. The SMN complex assembles the heptameric Sm protein core on small nuclear RNAs (snRNAs) and plays a critical role in the biogenesis of snRNPs, the major and essential components of mRNA splicing in eukaryotes. For its function, the SMN complex binds Sm proteins and snRNAs, which it distinguishes from other RNAs by specific features they contain. We show here that Gemin5, a 170 kDa WD-repeat protein, is the snRNA binding protein of the SMN complex. Gemin5 binds directly and specifically to the unique features, including the Sm site, of snRNAs. Reduction of Gemin5 results in reduced capacity of the SMN complex to bind snRNAs and to assemble Sm cores. Gemin5 therefore functions as the factor that allows the SMN complex to distinguish snRNAs from other cellular RNAs for snRNP biogenesis.

[1]  J. Steitz,et al.  Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[2]  G. Dreyfuss,et al.  Specific Sequences of the Sm and Sm-like (Lsm) Proteins Mediate Their Interaction with the Spinal Muscular Atrophy Disease Gene Product (SMN)* , 2000, The Journal of Biological Chemistry.

[3]  M. Mann,et al.  Purification of Native Survival of Motor Neurons Complexes and Identification of Gemin6 as a Novel Component* , 2002, The Journal of Biological Chemistry.

[4]  K. Nagai,et al.  Crystal Structures of Two Sm Protein Complexes and Their Implications for the Assembly of the Spliceosomal snRNPs , 1999, Cell.

[5]  Arnold Munnich,et al.  Correlation between severity and SMN protein level in spinal muscular atrophy , 1997, Nature Genetics.

[6]  T. Crawford,et al.  The survival motor neuron protein in spinal muscular atrophy. , 1997, Human molecular genetics.

[7]  Livio Pellizzoni,et al.  Identification and Characterization of Gemin7, a Novel Component of the Survival of Motor Neuron Complex* , 2002, The Journal of Biological Chemistry.

[8]  J. Yong,et al.  The Survival of Motor Neurons Protein Determines the Capacity for snRNP Assembly: Biochemical Deficiency in Spinal Muscular Atrophy , 2005, Molecular and Cellular Biology.

[9]  G. Dreyfuss,et al.  A novel nuclear structure containing the survival of motor neurons protein. , 1996, The EMBO journal.

[10]  G. Dreyfuss,et al.  The SMN–SIP1 Complex Has an Essential Role in Spliceosomal snRNP Biogenesis , 1997, Cell.

[11]  M. Mann,et al.  Gemin5, a Novel WD Repeat Protein Component of the SMN Complex That Binds Sm Proteins* , 2002, The Journal of Biological Chemistry.

[12]  J. Weissenbach,et al.  Identification and characterization of a spinal muscular atrophy-determining gene , 1995, Cell.

[13]  C. Will,et al.  Spliceosomal UsnRNP biogenesis, structure and function. , 2001, Current opinion in cell biology.

[14]  Temple F. Smith,et al.  The WD repeat: a common architecture for diverse functions. , 1999, Trends in biochemical sciences.

[15]  G. Dreyfuss,et al.  The SMN complex, an assemblyosome of ribonucleoproteins. , 2002, Current opinion in cell biology.

[16]  Jeongsik Yong,et al.  Specific Sequence Features, Recognized by the SMN Complex, Identify snRNAs and Determine Their Fate as snRNPs , 2005, Molecular and Cellular Biology.

[17]  Utz Fischer,et al.  Unique Sm core structure of U7 snRNPs: assembly by a specialized SMN complex and the role of a new component, Lsm11, in histone RNA processing. , 2003, Genes & development.

[18]  J. Yong,et al.  Essential Role for the SMN Complex in the Specificity of snRNP Assembly , 2002, Science.

[19]  H. Stark,et al.  The Sm domain is an ancient RNA-binding motif with oligo(U) specificity , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Shevchenko,et al.  Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems. , 1999, The Journal of cell biology.

[21]  J. Rappsilber,et al.  Unrip is a component of SMN complexes active in snRNP assembly , 2005, FEBS letters.

[22]  G. Dreyfuss,et al.  The Spinal Muscular Atrophy Disease Gene Product, SMN, and Its Associated Protein SIP1 Are in a Complex with Spliceosomal snRNP Proteins , 1997, Cell.

[23]  A. Shevchenko,et al.  Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli. , 2000, The Journal of cell biology.

[24]  J. Yong,et al.  snRNAs Contain Specific SMN-Binding Domains That Are Essential for snRNP Assembly , 2004, Molecular and Cellular Biology.

[25]  Holger Stark,et al.  Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle , 2001, Nature.

[26]  G. Meister,et al.  A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs , 2001, Nature Cell Biology.

[27]  T. Nilsen The spliceosome: the most complex macromolecular machine in the cell? , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[28]  J. Yong,et al.  Sequence‐specific interaction of U1 snRNA with the SMN complex , 2002, The EMBO journal.

[29]  G. Dreyfuss,et al.  Gemins modulate the expression and activity of the SMN complex. , 2005, Human molecular genetics.

[30]  J. Yong,et al.  Lymphotropic Herpesvirus saimiri Uses the SMN Complex To Assemble Sm Cores on Its Small RNAs , 2005, Molecular and Cellular Biology.

[31]  Raman Nambudripad,et al.  The ancient regulatory-protein family of WD-repeat proteins , 1994, Nature.