The SMN Tudor SIM-like domain is key to SmD1 and coilin interactions and to Cajal body biogenesis

Tapia, Olga; Lafarga, Vanesa; Bengoechea, Rocío; Palanca, Ana; Lafarga, Miguel; Berciano, Marı́a T.

doi:10.1242/jcs.138537

Cited by 20 publications

(26 citation statements)

References 35 publications

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“…The critical function that is affected in SMA is snRNP assembly, and it is well known that the snRNP biogenesis pathway involves four steps: (A) SMN oligomerization [22], (B) SMN interaction with Gemin proteins [27], (C) SMN binding to the Sm proteins of snRNPs, which are key constituents of spliceosomes [15], (D) SMN-coilin interaction in Cajal bodies [5], the nuclear organelles involved in the maturation of spliceosomal snRNPs.…”

Section: Resultsmentioning

confidence: 99%

How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?

2017

PLoS ONE

123

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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with dysfunctional α-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss (∼95% of SMA cases) or mutation (∼5% of SMA cases) of the survival motor neuron 1 gene SMN1. As the product of SMN1, SMN is a component of the SMN complex, and is also involved in the biosynthesis of the small nuclear ribonucleoproteins (snRNPs), which play critical roles in pre-mRNA splicing in the pathogenesis of SMA. To investigate how SMA-linked mutations of SMN1 lead to structural/functional deficiency of SMN, a set of computational analysis of SMN-related structures were conducted and are described in this article. Of extraordinary interest, the structural analysis highlights three SMN residues (Asp44, Glu134 and Gln136) with SMA-linked missense mutations, which cause disruptions of electrostatic interactions for Asp44, Glu134 and Gln136, and result in three functionally deficient SMA-linked SMN mutants, Asp44Val, Glu134Lys and Gln136Glu. From the computational analysis, it is also possible that SMN’s Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface.

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Section: Resultsmentioning

confidence: 99%

How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?

2017

PLoS ONE

123

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“…Recent work has shown that SMN is modified by SUMO1 at residue K119. 62 Sumoylated SMN is not enriched in the CB, which contains the desumoylation enzyme USPL1. This suggests that desumoylation of SMN takes place in the CB.…”

Section: How Does Modification Impact Smn's Cb Activity?mentioning

confidence: 97%

Towards an understanding of regulating Cajal body activity by protein modification

Hebert

Poole

2016

RNA Biology

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The biogenesis of small nuclear ribonucleoproteins (snRNPs), small Cajal body-specific RNPs (scaRNPs), small nucleolar RNPs (snoRNPs) and the telomerase RNP involves Cajal bodies (CBs). Although many components enriched in the CB contain post-translational modifications (PTMs), little is known about how these modifications impact individual protein function within the CB and, in concert with other modified factors, collectively regulate CB activity. Since all components of the CB also reside in other cellular locations, it is also important that we understand how PTMs affect the subcellular localization of CB components. In this review, we explore the current knowledge of PTMs on the activity of proteins known to enrich in CBs in an effort to highlight current progress as well as illuminate paths for future investigation.

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“…[91][92][93][94][95] In addition to overall protein levels, post-translational modifications (PTMs) of resident proteins, including SMN and coilin, are almost certainly important for establishing and maintaining inter-and intra-molecular interactions within Cajal bodies. [96][97][98][99][100] Disruption of these PTMs can result in mislocalization of SMN and alterations in Cajal body integrity. These and other factors will need to be addressed by future studies.…”

Section: Inter-and Intra-molecular Interactions Within the Cajal Bodymentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

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The SMN Tudor SIM-like domain is key to SmD1 and coilin interactions and to Cajal body biogenesis

Cited by 20 publications

References 35 publications

How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?

How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?

Towards an understanding of regulating Cajal body activity by protein modification

SMN - A chaperone for nuclear RNP social occasions?

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