Cryo-EM structure of the CBC-ALYREF complex
Bradley P Clarke1, Alexia E Angelos1, Menghan Mei1
1Department of Biochemistry, Vanderbilt University School of Medicine Basic Sciences, Nashville, United States.
Elife
|September 16, 2024
Summary
The nuclear cap binding complex (CBC) recruits mRNA export factors like ALYREF. This study reveals the CBC-ALYREF structure, detailing how ALYREF interacts with CBC to facilitate mRNA export.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Eukaryotic RNAs transcribed by RNA Pol II undergo 5' end 7-methylguanosine (m7G) capping.
- The nuclear cap binding complex (CBC) recognizes the m7G cap and is crucial for mRNA metabolism, including export.
- CBC interacts with ALYREF to link the TREX complex for mRNA export, but the mechanism is unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of CBC-mediated mRNA export recruitment.
- To determine the structural basis of the interaction between CBC and the mRNA export factor ALYREF.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine the structure of the CBC-ALYREF complex.
- Structural analysis and comparison with related cellular complexes.
Main Results:
- The first structure of the CBC in complex with ALYREF was determined.
- The RRM domain of ALYREF directly contacts both NCBP1 and NCBP2 subunits of the CBC.
- Structural insights into the coordinated roles of CBC and ALYREF in mRNA processing.
Conclusions:
- The CBC-ALYREF structure provides a molecular understanding of mRNA export initiation.
- This finding clarifies how the CBC facilitates the recruitment of export machinery via ALYREF.
- The study offers insights into the integration of transcription, splicing, and export pathways.
