Splicing factor U1-70K interacts with the SMN complex and is required for nuclear Gem integrity

Stejskalová, Eva; Staněk, David

doi:10.1242/jcs.155838

Cited by 17 publications

(15 citation statements)

References 38 publications

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“…84 Given its recently described role in human U1 snRNP assembly, U1-70K protein might be considered as an auxiliary member of the SMN complex. 85 Notably, a decrease in SMN protein levels (and thus an increase in SMA severity) is correlated with the loss of SMN nuclear foci.…”

Section: Nuclear Functions Of the Smn Complexmentioning

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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Section: Nuclear Functions Of the Smn Complexmentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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“…By contrast, K-MCDs from the nonsense mediated decay factor UPF2 172 We next sought to examine R-MCD function in the full-length spliceosome 188 component U1-70k. U1-70k localizes to the speckles and foci corresponding to snRNP 189 assembly bodies known as nuclear GEMs (Stejskalová and Staněk, 2014;Verheijen 190 et al, 1986). In addition to the R-MCD examined above (MCD1), U1-70k contains a 191 second smaller R-MCD (MCD2) ( Figure 3A…”

Section: Naturally Occurring Mcds Promote Nuclear Speckle Assembly 152mentioning

confidence: 99%

Arginine-enriched mixed-charge domains provide cohesion for nuclear speckle condensation

Greig

Nguyen

Lee

et al. 2019

Preprint

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15Low-complexity protein domains promote the formation of various biomolecular 16condensates. However, in many cases, the precise sequence features governing 17 condensate formation and identity remain unclear. Here, we investigate the role of 18 intrinsically disordered mixed-charge domains (MCDs) in nuclear speckle 19 condensation. Proteins composed exclusively of arginine/aspartic-acid dipeptide 20 repeats undergo length-dependent condensation and speckle incorporation. 21Substituting arginine with lysine in synthetic and natural speckle-associated MCDs 22 abolishes these activities, identifying a key role for multivalent contacts through 23 arginine's guanidinium ion. MCDs can synergise with a speckle-associated RNA 24 recognition motif to promote speckle specificity and residence. MCD behaviour is 25 tuneable through net-charge: increasing negative charge abolishes condensation and 26 speckle incorporation. By contrast, increasing positive charge through arginine leads 27 to enhanced condensation, speckle enlargement, decreased splicing factor mobility, 28 and defective mRNA export. Together, these results identify key sequence 29 determinants of MCD-promoted speckle condensation, and link the speckle's dynamic 30 material properties with function in mRNA processing. 31 32 33 34 2015; Nott et al., 2015; Patel et al., 2015). Multivalent interactions among repetitive 58 protein-protein or protein-RNA interaction domains / motifs are the key determinants 59 of LLPS (Dennis, 2015; Fung et al., 2018). Multivalent contacts can be achieved with 60 tandem repeats of folded domains (Li et al., 2012), through low-complexity (LC) 61intrinsically disordered regions (IDRs) (Halfmann, 2016;Lin et al., 2015; Mittag and 62 Parker, 2018), or a combination of the two (Mitrea et al., 2016; Zhang et al., 2015). In 63 these systems, individual contacts are relatively weak. However, with increasing 64 valence, the combined effect of many weak interactions overcome the entropic cost of 65 (Hyman et al., 2014). In many cases LC-IDRs have been shown to be necessary 66 and sufficient for LLPS. This raises key questions regarding the types of residues that 67 promote intermolecular contacts, and the extent to which these determine condensate 68 LLPSResults 103 104 Mixed-charge domains (MCDs) undergo condensation and localize to nuclear 105 speckles 106We previously showed that an arginine and aspartic acid (RD)-enriched MCD 107 from the fungal SPA-5 (SPA-5 MCD ) protein forms a viscoelastic hydrogel. In the fungus, 108 this activity is associated with the formation of cytoplasmic plugs that gate cell-to-cell 109 channels (Lai et al., 2012). To explore the role of such sequences in animal cells, we 110 expressed SPA-5 MCD as an mGFP-fusion in HeLa cells (SPA-5 MCD -mGFP). In this 111 context, SPA-5 MCD -mGFP accumulates in nuclear speckles as revealed by co-112 localization with the speckle marker serine/arginine-rich splicing factor 1 (SRSF1) 113( Figures 1A and S1A). SPA-5 MCD is enriched in RD dipeptide repeats. However, it als...

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“…Less is known about chaperons involved in U1 and U2 snRNP assembly. U1-specific SNRNP70 (U1-70K) has been recently found to interact with the SMN complex and promote Sm ring assembly specifically on the U1 snRNA, 36,37 which suggests that SNRNP70 interacts with U1 snRNA in the cytoplasm. Both U1 snRNA and SNRNP70 have been detected in gems, nuclear structures that are rich in SMN complexes 36 .…”

Section: Biogenesis Of Snrnpsmentioning

confidence: 99%

“…U1-specific SNRNP70 (U1-70K) has been recently found to interact with the SMN complex and promote Sm ring assembly specifically on the U1 snRNA, 36,37 which suggests that SNRNP70 interacts with U1 snRNA in the cytoplasm. Both U1 snRNA and SNRNP70 have been detected in gems, nuclear structures that are rich in SMN complexes 36 . SNRNP70 interacts with the SMN complex also in the cell nucleus suggesting that nuclear SMN is involved in U1 snRNP maturation and/or recycling 36,38 .…”

Section: Biogenesis Of Snrnpsmentioning

confidence: 99%

“…Both U1 snRNA and SNRNP70 have been detected in gems, nuclear structures that are rich in SMN complexes 36 . SNRNP70 interacts with the SMN complex also in the cell nucleus suggesting that nuclear SMN is involved in U1 snRNP maturation and/or recycling 36,38 . Alternatively, nuclear SNRNP70-SMN complexes could represent post-imported U1 particles.…”

Section: Biogenesis Of Snrnpsmentioning

confidence: 99%

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Cajal bodies and snRNPs - friends with benefits

Staněk

2016

RNA Biology

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Spliceosomal snRNPs are complex particles that proceed through a fascinating maturation pathway. Several steps of this pathway are closely linked to nuclear non-membrane structures called Cajal bodies. In this review, I summarize the last 20 y of research in this field. I primarily focus on snRNP biogenesis, specifically on the steps that involve Cajal bodies. I also evaluate the contribution of the Cajal body in snRNP quality control and discuss the role of snRNPs in Cajal body formation.

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Splicing factor U1-70K interacts with the SMN complex and is required for nuclear Gem integrity

Cited by 17 publications

References 38 publications

SMN - A chaperone for nuclear RNP social occasions?

SMN - A chaperone for nuclear RNP social occasions?

Arginine-enriched mixed-charge domains provide cohesion for nuclear speckle condensation

Cajal bodies and snRNPs - friends with benefits

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