Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions

ABSTRACT: Transcriptome analysis of specific mRNA interacting with KIF1C-GFP in HeLa Cells. RNA localization and local translation are involved in a wide range of cellular functions. In mammals, a class of mRNAs localize to cytoplasmic protrusions in an APC dependent manner, with important roles during cell migration. Here, we investigated this localization mechanism. We found that the KIF1C motor interacts with many APC-dependent mRNAs and is required for their localization. Live cell imaging of localizing mRNAs further revealed rapid, active transport of single mRNAs over long distances, and showed that this requires both microtubules and KIF1C. Moreover, two color imaging directly revealed single mRNAs transported by single KIF1C motors, with the 3’UTR of localized mRNAs being sufficient to trigger KIF1C-dependent RNA transport and localization. These results reveal a general RNA transport pathway in mammalian cells, in which the KIF1C motor transports RNAs to cytoplasmic protrusions. Interestingly, KIF1C also transported its own mRNA suggesting a possible feedback loop acting at the level of mRNA transport.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161316 | GEO | 2020/11/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA localization to protrusions of mouse melanoma YUMM1.7 cells.

Project description:Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In non-neuronal cells, a subset of mRNAs localize to cell protrusions and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show that Kif1c mRNA localization does not regulate KIF1C protein abundance, distribution, οr ability to traffic other mRNAs. Conversely, robust Kif1c mRNA localization is required for directed cell migration. We used mass spectrometry to identify binding partners of endogenous KIF1C, which revealed dramatic dysregulation of the number and identity of KIF1C interactors in response to Kif1c mRNA mis-localization. These results therefore uncovered a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein-protein interactions. We anticipate that this mechanism is not limited to Kif1c and is likely to be a general principle used by protrusion-enriched mRNAs in non-neuronal cells.

2023-02-24 | GSE219089 | GEO

The protein complex of kinesin motor KIF1C and its hereditary spastic paraplegia associated mutant G102A

Project description:Regulated local translation, RNA transport and protein localization are critical for spatio-temporal gene expression in neurons. The localization of mRNA and subsequent local protein synthesis contribute to neuronal functions like synaptogenesis, synapse pruning, axon guidance, axonal regeneration and synaptic plasticity. Thus, mutations in motor proteins and subsequent cargo transport failure lead to motoneuron diseases. The kinesin family member 1 C has been shown to play a role in different cargo transport alongside the microtubule network, but the pathomechanisms behind KIF1C deficiency mediated motoneuron diseases has not been deciphered yet. Additionally, the exon junction complex has been suggested as a molecular link between splicing and cytoplasmic mRNA localization and local translation. Here we identified KIF1C as a EJC transporter in neuronal cells. We investigated the KIF1C proteome in differentiated SH-SY5Y cells and found an interaction of KIF1C with EJC components and other RNA-binding proteins in KIF1C overexpressing SH-SY5Y cells. The interaction could be validated via immunoprecipitation and an endogenous eIF4A3 co-immunoprecipitation. The co-localization of eIF4A3 and RBM8A with wildtpye KIF1C at protrusions of SH-SY5Ys further confirms the interaction. The mislocalization of eIF4A3 and RMB8A due to KIF1C mutation suggests a transport of the EJC by KIF1C. Furthermore, the interaction of KIF1C with PABPC1 and EJC components is RNA mediated. We additionally demonstrate via complex capture with KIF1C overexpressing HEK293 cells that KIF1C interacts with RNA itself. We therefore suggest the interaction of KIF1C not only with the EJC, but with a complex containing RNA and the EJC. Hence KIF1C is a transporter of mRNA and the EJC.

2023-12-28 | PXD037387 | Pride

The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions

Project description:The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions

| PRJNA677869 | ENA

RNAs enriched at protrusions of control or APC knockdown fibroblasts

Project description:We used a fractionation scheme to isolate protrusions and cell bodies from control or APC knockdown fibroblasts, which were induced to extend protrusions in response to addition of lysophosphatidic acid (LPA). Four replicate protrusion and cell body samples for each cell type were analyzed by RNA-Seq. To identify RNAs enriched in protrusions, a protrusion/cell body ratio was calculated. We find that ca. 7% of detected RNAs were enriched in protrusions of control cells. Knockdown of APC reduced the protrusion enrichement of a subset of these RNAs, indicating that they are dependent on APC for their localization. Localization of the remaining RNAs was not significantly affected upon APC knockdown suggesting that their localization is mediated by an APC-independent mechanism.

2017-10-11 | GSE82229 | GEO

PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport

Project description:The kinesin-3 KIF1C is a fast organelle transporter implicated in the transport of dense core vesicles in neurons and the delivery of integrins to cell adhesions. Here we report the mechanisms of autoinhibition and release that control the activity of KIF1C. We show that the microtubule binding surface of KIF1C motor domain interacts with its stalk and that these autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21. The FERM domain of PTPN21 stimulates dense core vesicle transport in primary hippocampal neurons and rescues integrin trafficking in KIF1C-depleted cells. In vitro, human full-length KIF1C is a processive, plus-end directed motor. Its landing rate onto microtubules increases in the presence of either PTPN21 FERM domain or the cargo adapter Hook3 that binds the same region of KIF1C tail. This autoinhibition release mechanism allows cargo-activated transport and might enable motors to participate in bidirectional cargo transport without undertaking a tug-of-war.

2019-06-24 | PXD013939 | Pride

Transcriptome-wide view of endosomal mRNP transport [RNA-Seq]

Project description:Spatiotemporal protein expression is mediated by active transport and local translation of mRNAs. Key factors of the transport machinery are RNA-binding proteins (RBPs) that recognise mRNAs as cargo for motor-based transport. However, a global view of transported mRNAs with cognate RBP binding sites is missing. Here, we cast a transcriptome-wide view on endosomal mRNP transport in Ustilago maydis by studying the newly identified endosomal RBP Grp1 and the key transport RBP Rrm4 in a comparative iCLIP approach. This uncovered thousand of cargo mRNAs bound by both RBPs.

2018-12-10 | GSE109560 | GEO

Transcriptome-wide view of endosomal mRNP transport [iCLIP ]

2018-12-10 | GSE109557 | GEO

3' mRNA-seq of protrusions and cell bodies of BJ, PC-3M, RPE-1, U-87 and WM-266.4 cells

Project description:3' mRNA-seq of protrusions and cell bodies of a panel of normal and malignant cell lines. These data show that Ribosomal protein (RP) -mRNAs localization to cell protrusions is a conserved phenomenon.

2020-10-30 | E-MTAB-8470 | biostudies-arrayexpress

3' mRNA-seq of protrusions and cell bodies of non-transfected (nt) or LARP6 siRNA transfected MDA-MB231 cells

Project description:3' mRNA-seq of protrusions and cell bodies of nt or LARP6 siRNA transfected MDA-MB231 cells. These data show that Ribosomal protein (RP) -mRNAs localization to cell protrusions is mediated by LARP6.

2022-10-03 | E-MTAB-8472 | biostudies-arrayexpress

Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes

Project description:Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7’s interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7’s cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.

2024-01-24 | MSV000093914 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data