| 2011 |
NSrp70 (NSRP1/CCDC55) localizes to nuclear speckles and physically interacts with splicing factors SC35 and ASF/SF2; it modulates alternative splice site selection in vivo using CD44, Tra2β1, and Fas minigene reporters. The region spanning amino acids 290–471 is critical for speckle localization and SC35/ASF/SF2 binding, the N-terminal region (107–161) is essential for pre-mRNA splicing activity, and the C-terminal 10 amino acids (531–540), including RD at positions 536–537, constitute a novel nuclear localization signal. |
Co-immunoprecipitation, co-localization by confocal microscopy, minigene splicing reporter assays, deletion mutagenesis, NSrp70 knockout mice |
Nucleic acids research |
High |
21296756
|
| 2011 |
Knockout of the Nsrp1 (NSrp70) gene in mice results in a complete lack of progeny including fetal embryos, establishing that NSrp70 is essentially required for early embryonic development. |
Gene knockout in mice (loss-of-function) |
Nucleic acids research |
High |
21296756
|
| 2015 |
NSRP1 (CCDC55) physically interacts with RanBP9 and DISC1, and co-localizes with RanBP9 in the nucleus of human neuronal cells. NSRP1 also interacts with the cannabinoid receptor CNR1 and cannabinoid receptor-interacting protein CNRIP1a, as demonstrated by yeast two-hybrid screening and GST pull-down assay. |
Yeast two-hybrid screening, GST pull-down assay, confocal laser scanning microscopy |
Neuroscience |
Medium |
26475744
|
| 2016 |
Knockdown of NSrp70 in Xenopus embryos blocks gastrulation and convergent extension, and animal cap assays with activin A treatment show NSrp70 is required for dorsal mesoderm induction, with loss causing downregulation of dorsal mesoderm-specific genes. |
Morpholino knockdown in Xenopus, animal cap assay with activin A treatment, phenotypic readout of gastrulation and mesoderm markers |
Biochemical and biophysical research communications |
Medium |
27638308
|
| 2021 |
NSrp70 is selectively expressed in developing thymocytes and is highest at the double-positive (DP) stage. Conditional knockout (CD4Cre-driven Nsrp1 cKO) causes severe defects in T cell maturation to single-positive thymocytes due to insufficient TCR signaling and dysregulated cell growth/death. NSrp70 controls thymocyte cell cycle and survival by regulating alternative splicing of various RNA splicing factors including the oncogenic splicing factor SRSF1. |
Conditional knockout mouse (CD4Cre), RNA-seq and splicing profiling, flow cytometry of thymic subsets |
Nucleic acids research |
High |
34037780
|
| 2021 |
Biallelic loss-of-function frameshift variants in NSRP1 causing premature termination in the last exon are predicted to escape NMD and result in loss of the C-terminal nuclear localization signal required for NSRP1 function, establishing that NLS loss is a pathogenic mechanism in NSRP1-associated neurodevelopmental disorder. |
Exome sequencing, molecular analysis of mutant transcripts, prediction of NMD escape and NLS loss |
Genetics in medicine |
Medium |
34385670
|
| 2022 |
NSrp70 suppresses breast cancer metastasis by promoting inclusion of skipped exons in NUMB pre-mRNA (inhibiting skipped-exon alternative splicing of NUMB), leading to increased TGFβ receptor 1 (TβR1) degradation via the lysosome pathway and suppression of TGFβ/SMAD-mediated EMT. Direct binding between NSrp70 and NUMB pre-mRNA was confirmed by RNA pull-down and RNA immunoprecipitation. |
RNA-seq with AS bioinformatics, in vitro splicing assays, RNA pull-down, RNA immunoprecipitation, in vitro and in vivo functional assays (migration/invasion), proteomic screen |
Oncogene |
High |
35568738
|
| 2024 |
A missense variant p.Val532Glu in the nuclear localization signal of NSRP1 causes mislocalization of NSRP1 to the cytosol in HEK293T cells, confirming that the NLS (around Val532) is required for correct nuclear targeting of NSRP1. |
HEK293T transfection with GFP-tagged wild-type or mutant NSRP1, confocal microscopy for subcellular localization |
American journal of medical genetics. Part A |
Medium |
38808951
|
| 2024 |
NSRP1 knockdown in MCF7 breast cancer cells activates the IFN signaling pathway and elevates IRPS gene expression; mechanistically, NSRP1 controls alternative splicing of NSD2 such that its knockdown increases inclusion of NSD2 exon 2, which elevates NSD2 protein expression and thereby activates the IFN signaling pathway, conferring CDK4/6 inhibitor resistance. |
NSRP1 knockdown and overexpression in MCF7 cells, RNA-seq, alternative splicing analysis, CDK4/6 inhibitor sensitivity assays |
The Journal of biological chemistry |
Medium |
39667501
|