Co-evolution of spliceosomal disassembly interologs: crowning J-protein component with moonlighting RNA-binding activity

Raut, Sandeep; Yadav, Kirpa; Verma, Amit; Tak, Yogesh; Waiker, Prashant; Sahi, Chandan

doi:10.1007/s00294-018-0906-9

Cited by 7 publications

(18 citation statements)

References 63 publications

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“…DNAJC8 and DNAJC17 associated with distinct subunits of the spliceosome. DNAJC17 interacted with the U5 small nuclear ribonucleoprotein particle (snRNP) and the PRP19 complex, consistent with the role of its yeast ortholog Cwc23 in the late stages of splicing (Figures 4A and S4D) (Pascarella et al, 2018;Raut et al, 2019;Sahi et al, 2010). In contrast, the poorly characterized DNAJC8 interacted with the SF3b subcomplex, a component of the U2 snRNP that acts earlier in splicing (Figures 4A and S4D).…”

Section: Unique Specificities Of Jdpssupporting

confidence: 63%

Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains

et al. 2021

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Section: Unique Specificities Of Jdpssupporting

confidence: 63%

Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains

et al. 2021

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“…DNAJC17 is predicted to bind RNA through its RNA recognition motif (RRM). 14,15 However, attempts to isolate RNAs bound to either endogenous or overexpressed FLAG-tagged DNAJC17 were unsuccessful. Cells were lysed, subjected to FLAG-immunoprecipitation, and then total RNA was extracted and quantified through capillary electrophoresis.…”

Section: Resultsmentioning

confidence: 99%

The essential chaperone DNAJC17 activates HSP70 to coordinate RNA splicing and G2-M progression

Allegakoen,

Kwong,

Morales

et al. 2023

Preprint

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Molecular chaperones including the heat-shock protein 70-kilodalton (HSP70) family and the J-domain containing protein (JDP) co-chaperones maintain homeostatic balance in eukaryotic cells through regulation of the proteome. The expansive JDP family helps direct specific HSP70 functions, and yet loss of single JDP-encoding genes is widely tolerated by mammalian cells, suggesting a high degree of redundancy. By contrast, essential JDPs might carry out HSP70-independent functions or fill cell-context dependent, highly specialized roles within the proteostasis network. Using a genetic screen of DJPs in human cancer cell lines, we found the RNA recognition motif (RRM) containing DNAJC17 to be pan-essential and investigated the contribution of its structural domains to biochemical and cellular function. We found that the RRM exerts an auto-inhibitory effect on the ability of DNAJC17 to allosterically activate ATP hydrolysis by HSP70. The J-domain, but neither the RRM nor a distal C-terminal alpha helix are required to rescue cell viability after loss of endogenous DNAJC17. Knockdown of DNAJC17 leads to relatively few conserved changes in the abundance of individual mRNAs, but instead deranges gene expression through exon skipping, primarily of genes involved in cell cycle progression. Concordant with cell viability experiments, the C-terminal portions of DNAJC17 are dispensable for restoring splicing and G2-M progression. Overall, our findings identify essential cellular JDPs and suggest that diversification in JDP structure extends the HSP70-JDP system to control divergent processes such as RNA splicing. Future investigations into the structural basis for auto-inhibition of the DNAJC17 J-domain and the molecular regulation of splicing by these components may provide insights on how conserved biochemical mechanisms can be programmed to fill unique, non-redundant cellular roles and broaden the scope of the proteostasis network.

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“…This control may have evolved later in the evolution of the splicing machinery, because different organisms seem to have arrived at somewhat different solutions. The structures of the ILS from human, S. pombe , and S. cerevisiae and their genomes suggest that overlapping but divergent sets of proteins to block catalysis and promote Prp43 binding for disassembly (Raut et al 2019; Zhang et al 2019). Among these is the cwf19 protein from S. pombe and its human homolog CWF19L2, which carry a conserved domain that binds to and blocks the catalytic center (Yan et al 2015; Zhang et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Human and S. pombe homologs distantly related to S. cerevisiae Spp382/Ntr1 are not found in those ILS complexes, and Ntr2, an essential binding partner of Spp382/Ntr1, has no significant homolog in the S. pombe or human genome. The J-protein Cwc23 interacts with and supports the splicing function of Spp382/Ntr1, Ntr2, and Prp43 (Pandit et al 2009; Su et al 2018; Sahi et al 2010), but appears to have divergent functions in other organisms (Raut et al 2019). The protein compositions of ILS structure models from different organisms may differ due to varying stabilities and abundances of different states of the ILS found in each, and may not be strictly comparable.…”

Section: Discussionmentioning

confidence: 99%

Intron-lariat spliceosomes convert lariats to true circles: implications for intron transposition

Ares,

Igel,

Katzman

et al. 2024

Preprint

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Rare, full length circular intron RNAs distinct from lariats have been reported in several species, but their biogenesis is not understood. We envision and test a hypothesis for their formation using Saccharomyces cerevisiae, documenting full length and novel processed circular RNAs from multiple introns. Evidence implicates a previously undescribed catalytic activity of the intron-lariat spliceosome (ILS) in which the 3'-OH of the lariat tail (with optional trimming and adenylation by the nuclear 3' processing machinery) attacks the branch, joining the intron 3' end to the 5' splice site in a 3'-5' linked circle. Human U2 and U12 spliceosomes produce analogous full length and processed circles. Post-splicing catalytic activity of the spliceosome may promote intron transposition during eukaryotic genome evolution.

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Co-evolution of spliceosomal disassembly interologs: crowning J-protein component with moonlighting RNA-binding activity

Cited by 7 publications

References 63 publications

Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains

Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains

The essential chaperone DNAJC17 activates HSP70 to coordinate RNA splicing and G2-M progression

Intron-lariat spliceosomes convert lariats to true circles: implications for intron transposition

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