A KIF1C-CNBP motor-adaptor complex for trafficking mRNAs to cell protrusions
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Abstract:
mRNA localization to subcellular compartments is a widely used mechanism that functionally contributes to numerous processes. mRNA targeting can be achieved upon recognition of RNA cargo by molecular motors. However, our molecular understanding of how this is accomplished is limited, especially in higher organisms. We focus on a pathway that targets mRNAs to peripheral protrusions of mammalian cells and is important for cell migration. Trafficking occurs through active transport on microtubules, mediated by the KIF1C kinesin. Here, we identify the RNA-binding protein CNBP, as a factor required for mRNA localization to protrusions. CNBP binds directly to GA-rich sequences in the 3'UTR of protrusion targeted mRNAs. CNBP also interacts with KIF1C and is required for KIF1C recruitment to mRNAs and for their trafficking on microtubules to the periphery. This work provides a molecular mechanism for KIF1C recruitment to mRNA cargo and reveals a motor-adaptor complex for mRNA transport to cell protrusions.
Insights
Researchers discovered how messenger RNA (mRNA) travels to cell edges. The protein CNBP acts as an adaptor, linking mRNA to the KIF1C motor protein for transport along microtubules, crucial for cell migration.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- mRNA localization is vital for cellular functions, including cell migration.
- Molecular motors facilitate mRNA transport, but mechanisms in higher organisms are not fully understood.
- Transport to cell protrusions is critical for cell movement.
Purpose of the Study:
- To elucidate the molecular mechanism of mRNA targeting to mammalian cell protrusions.
- To identify factors involved in mRNA transport mediated by kinesin KIF1C.
- To understand the role of RNA-binding proteins in mRNA localization.
Main Methods:
- Identifying RNA-binding proteins interacting with specific mRNA targets.
- Investigating protein-protein interactions using co-immunoprecipitation.
- Analyzing mRNA localization and transport in mammalian cells via microscopy.
- Studying the role of CNBP in KIF1C recruitment and microtubule-based transport.
Main Results:
- The RNA-binding protein CNBP directly binds GA-rich sequences in the 3' untranslated region (3'UTR) of protrusion-targeted mRNAs.
- CNBP interacts with the kinesin motor KIF1C.
- CNBP is essential for recruiting KIF1C to mRNA cargo.
- CNBP facilitates KIF1C-mediated trafficking of mRNAs along microtubules to cell periphery.
Conclusions:
- CNBP acts as a crucial adaptor protein linking mRNA cargo to the KIF1C motor.
- This study reveals a novel motor-adaptor complex for mRNA transport to cell protrusions.
- The findings provide a molecular mechanism for KIF1C recruitment to mRNA and its subsequent transport, impacting cell migration.
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