scholarly journals Survival Motor Neuron Function in Motor Axons Is Independent of Functions Required for Small Nuclear Ribonucleoprotein Biogenesis

2006 ◽  
Vol 26 (43) ◽  
pp. 11014-11022 ◽  
Author(s):  
T. L. Carrel ◽  
M. L. McWhorter ◽  
E. Workman ◽  
H. Zhang ◽  
E. C. Wolstencroft ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Survival Motor Neuron ◽  
Motor Axons ◽  
Small Nuclear Ribonucleoprotein ◽  
Neuron Function ◽  
Nuclear Ribonucleoprotein

scholarly journals Role of Survival Motor Neuron Complex Components in Small Nuclear Ribonucleoprotein Assembly

2009 ◽  
Vol 284 (21) ◽  
pp. 14609-14617 ◽  
Author(s):  
Chihiro Ogawa ◽  
Kengo Usui ◽  
Fuyu Ito ◽  
Masayoshi Itoh ◽  
Yoshihide Hayashizaki ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Survival Motor Neuron ◽  
Small Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein ◽  
Complex Components ◽  
Ribonucleoprotein Assembly

scholarly journals Gemin8 Is a Novel Component of the Survival Motor Neuron Complex and Functions in Small Nuclear Ribonucleoprotein Assembly

2006 ◽  
Vol 281 (12) ◽  
pp. 8126-8134 ◽  
Author(s):  
Claudia Carissimi ◽  
Luciano Saieva ◽  
Jennifer Baccon ◽  
Pieranna Chiarella ◽  
Alessio Maiolica ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Survival Motor Neuron ◽  
Small Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein ◽  
Ribonucleoprotein Assembly

scholarly journals Identification and characterization ofDrosophilaSnurportin reveals a role for the import receptor Moleskin/importin-7 in snRNP biogenesis

2013 ◽  
Vol 24 (18) ◽  
pp. 2932-2942 ◽  
Author(s):  
Amanda Hicks Natalizio ◽  
A. Gregory Matera
Keyword(s):  
Fruit Fly ◽  
Survival Motor Neuron ◽  
Cajal Body ◽  
Small Nuclear Ribonucleoprotein ◽  
Small Nuclear Rnas ◽  
Assembly Factor ◽  
Nuclear Ribonucleoprotein ◽  
Identification And Characterization ◽  
Transport Receptor ◽  
Import Receptor

Nuclear import is an essential step in small nuclear ribonucleoprotein (snRNP) biogenesis. Snurportin1 (SPN1), the import adaptor, binds to trimethylguanosine (TMG) caps on spliceosomal small nuclear RNAs. Previous studies indicated that vertebrate snRNP import requires importin-β, the transport receptor that binds directly to SPN1. We identify CG42303/snup as the Drosophila orthologue of human snurportin1 (SNUPN). Of interest, the importin-β binding (IBB) domain of SPN1, which is essential for TMG cap–mediated snRNP import in humans, is not well conserved in flies. Consistent with its lack of an IBB domain, we find that Drosophila SNUP (dSNUP) does not interact with Ketel/importin-β. Fruit fly snRNPs also fail to bind Ketel; however, the importin-7 orthologue Moleskin (Msk) physically associates with both dSNUP and spliceosomal snRNPs and localizes to nuclear Cajal bodies. Strikingly, we find that msk-null mutants are depleted of the snRNP assembly factor, survival motor neuron, and the Cajal body marker, coilin. Consistent with a loss of snRNP import function, long-lived msk larvae show an accumulation of TMG cap signal in the cytoplasm. These data indicate that Ketel/importin-β does not play a significant role in Drosophila snRNP import and demonstrate a crucial function for Msk in snRNP biogenesis.

scholarly journals Conditional deletion of SMN in cell culture identifies functional SMN alleles

2020 ◽  
Author(s):  
Anton J Blatnik ◽  
Vicki L McGovern ◽  
Thanh T Le ◽  
Chitra C Iyer ◽  
Brian K Kaspar ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Mouse Embryonic Fibroblast ◽  
Survival Motor Neuron ◽  
Conditional Deletion ◽  
Small Nuclear Ribonucleoprotein ◽  
Missense Mutant ◽  
Smn Protein ◽  
Nuclear Ribonucleoprotein ◽  
First Time ◽  
Embryonic Fibroblast

Abstract Spinal muscular atrophy (SMA) is caused by mutation or deletion of survival motor neuron 1 (SMN1) and retention of SMN2 leading to SMN protein deficiency. We developed an immortalized mouse embryonic fibroblast (iMEF) line in which full-length wild-type Smn (flwt-Smn) can be conditionally deleted using Cre recombinase. iMEFs lacking flwt-Smn are not viable. We tested the SMA patient SMN1 missense mutation alleles A2G, D44V, A111G, E134K and T274I in these cells to determine which human SMN (huSMN) mutant alleles can function in the absence of flwt-Smn. All missense mutant alleles failed to rescue survival in the conditionally deleted iMEFs. Thus, the function lost by these mutations is essential to cell survival. However, co-expression of two different huSMN missense mutants can rescue iMEF survival and small nuclear ribonucleoprotein (snRNP) assembly, demonstrating intragenic complementation of SMN alleles. In addition, we show that a Smn protein lacking exon 2B can rescue iMEF survival and snRNP assembly in the absence of flwt-Smn, indicating exon 2B is not required for the essential function of Smn. For the first time, using this novel cell line, we can assay the function of SMN alleles in the complete absence of flwt-Smn.

scholarly journals Impaired spliceosomal UsnRNP assembly leads to Sm mRNA down-regulation and Sm protein degradation

2017 ◽  
Vol 216 (8) ◽  
pp. 2391-2407 ◽  
Author(s):  
Archana Bairavasundaram Prusty ◽  
Rajyalakshmi Meduri ◽  
Bhupesh Kumar Prusty ◽  
Jens Vanselow ◽  
Andreas Schlosser ◽  
...  
Keyword(s):  
Survival Motor Neuron ◽  
Sm Proteins ◽  
Down Regulation ◽  
Small Nuclear Ribonucleoprotein ◽  
Smn Complex ◽  
Assembly Factors ◽  
Nuclear Ribonucleoprotein ◽  
Contrast Reduction ◽  
Sm Protein

Specialized assembly factors facilitate the formation of many macromolecular complexes in vivo. The formation of Sm core structures of spliceosomal U-rich small nuclear ribonucleoprotein particles (UsnRNPs) requires assembly factors united in protein arginine methyltransferase 5 (PRMT5) and survival motor neuron (SMN) complexes. We demonstrate that perturbations of this assembly machinery trigger complex cellular responses that prevent aggregation of unassembled Sm proteins. Inactivation of the SMN complex results in the initial tailback of Sm proteins on the PRMT5 complex, followed by down-regulation of their encoding mRNAs. In contrast, reduction of pICln, a PRMT5 complex subunit, leads to the retention of newly synthesized Sm proteins on ribosomes and their subsequent lysosomal degradation. Overexpression of Sm proteins under these conditions results in a surplus of Sm proteins over pICln, promoting their aggregation. Our studies identify an elaborate safeguarding system that prevents individual Sm proteins from aggregating, contributing to cellular UsnRNP homeostasis.

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