Cryo-EM structure of the CBC-ALYREF complex

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Eukaryotic RNAs undergo 5' end modification with a 7-methylguanosine (m7G) cap.
• The nuclear cap binding complex (CBC) recognizes the m7G cap and is crucial for mRNA metabolism.
• CBC mediates mRNA export by interacting with ALYREF, a component of the TRanscription and EXport (TREX) complex.

Purpose of the Study:

• To elucidate the molecular mechanism of CBC-mediated recruitment of mRNA export machinery.
• To determine the structural basis of the interaction between CBC and ALYREF.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine the structure of the CBC-ALYREF complex.

Main Results:

• The first structure of the CBC in complex with the mRNA export factor ALYREF was determined.
• The cryo-EM structure revealed direct contacts between the RRM domain of ALYREF and both NCBP1 and NCBP2 subunits of the CBC.
• Structural comparisons provided insights into coordinated events in mRNA transcription, splicing, and export.

Conclusions:

• The structure provides a molecular understanding of how CBC recruits ALYREF for mRNA export.
• This finding contributes to understanding the intricate processes of mRNA metabolism and transport in eukaryotes.