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The Spinal Muscular Atrophy Disease Gene Product, Smn

The Spinal Muscular Atrophy Disease Gene Product, Smn The spliceosomal snRNAs U1, U2, U4, and U5 are synthesized in the nucleus, exported to the cytoplasm to assemble with Sm proteins, and reimported to the nucleus as ribonucleoprotein particles. Recently, two novel proteins involved in biogenesis of small nuclear ribonucleoproteins (snRNPs) were identified, the Spinal muscular atrophy disease gene product (SMN) and its associated protein SIP1. It was previously reported that in HeLa cells, SMN and SIP1 form discrete foci located next to Cajal (coiled) bodies, the so-called “gemini of coiled bodies” or “gems.” An intriguing feature of gems is that they do not appear to contain snRNPs. Here we show that gems are present in a variable but small proportion of rapidly proliferating cells in culture. In the vast majority of cultured cells and in all primary neurons analyzed, SMN and SIP1 colocalize precisely with snRNPs in the Cajal body. The presence of SMN and SIP1 in Cajal bodies is confirmed by immunoelectron microscopy and by microinjection of antibodies that interfere with the integrity of the structure. The association of SMN with snRNPs and coilin persists during cell division, but at the end of mitosis there is a lag period between assembly of new Cajal bodies in the nucleus and detection of SMN in these structures, suggesting that SMN is targeted to preformed Cajal bodies. Finally, treatment of cells with leptomycin B (a drug that blocks export of U snRNAs to the cytoplasm and consequently import of new snRNPs into the nucleus) is shown to deplete snRNPs (but not SMN or SIP1) from the Cajal body. This suggests that snRNPs flow through the Cajal body during their biogenesis pathway. Cajal (coiled) body leptomycin B nucleocytoplasmic transport SMN protein spliceosomal small nuclear ribonucleoproteins Footnotes 1.used in this paper: m3G, 2,2,7-trimethylguanosine cap; SIP1, SMN interacting protein 1; SMN, survival motor neurons; snRNP, small nuclear ribonucleoprotein Submitted: 26 August 1999 Revision requested 23 September 1999 Accepted: 30 September 1999 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

The Spinal Muscular Atrophy Disease Gene Product, Smn

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References (87)

Publisher
Rockefeller University Press
Copyright
© 1999 The Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.147.4.715
Publisher site
See Article on Publisher Site

Abstract

The spliceosomal snRNAs U1, U2, U4, and U5 are synthesized in the nucleus, exported to the cytoplasm to assemble with Sm proteins, and reimported to the nucleus as ribonucleoprotein particles. Recently, two novel proteins involved in biogenesis of small nuclear ribonucleoproteins (snRNPs) were identified, the Spinal muscular atrophy disease gene product (SMN) and its associated protein SIP1. It was previously reported that in HeLa cells, SMN and SIP1 form discrete foci located next to Cajal (coiled) bodies, the so-called “gemini of coiled bodies” or “gems.” An intriguing feature of gems is that they do not appear to contain snRNPs. Here we show that gems are present in a variable but small proportion of rapidly proliferating cells in culture. In the vast majority of cultured cells and in all primary neurons analyzed, SMN and SIP1 colocalize precisely with snRNPs in the Cajal body. The presence of SMN and SIP1 in Cajal bodies is confirmed by immunoelectron microscopy and by microinjection of antibodies that interfere with the integrity of the structure. The association of SMN with snRNPs and coilin persists during cell division, but at the end of mitosis there is a lag period between assembly of new Cajal bodies in the nucleus and detection of SMN in these structures, suggesting that SMN is targeted to preformed Cajal bodies. Finally, treatment of cells with leptomycin B (a drug that blocks export of U snRNAs to the cytoplasm and consequently import of new snRNPs into the nucleus) is shown to deplete snRNPs (but not SMN or SIP1) from the Cajal body. This suggests that snRNPs flow through the Cajal body during their biogenesis pathway. Cajal (coiled) body leptomycin B nucleocytoplasmic transport SMN protein spliceosomal small nuclear ribonucleoproteins Footnotes 1.used in this paper: m3G, 2,2,7-trimethylguanosine cap; SIP1, SMN interacting protein 1; SMN, survival motor neurons; snRNP, small nuclear ribonucleoprotein Submitted: 26 August 1999 Revision requested 23 September 1999 Accepted: 30 September 1999

Journal

The Journal of Cell Biology – Rockefeller University Press

Published: Nov 15, 1999

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