Nuclear factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA

Area of Science:

• Molecular Biology
• Structural Biology
• Gene Regulation

Background:

• Nuclear factors 90 and 45 (NF90/NF45) form a complex controlling gene expression post-transcriptionally.
• NF90 contains tandem dsRNA-binding domains (dsRBDs) essential for its RNA-binding function.
• Known RNA targets include mRNA 3' UTRs and non-coding RNAs.

Purpose of the Study:

• To elucidate the structural basis of dsRNA recognition by the NF90 protein.
• To compare the dsRNA-binding mechanism of NF90 with other dsRNA-binding proteins.

Main Methods:

• X-ray crystallography was used to determine the structure of NF90's tandem dsRBDs bound to dsRNA.
• Structural comparison with known dsRNA-binding proteins was performed.

Main Results:

• The crystal structure of NF90 tandem dsRBDs complexed with dsRNA was determined.
• NF90 dsRBDs exhibit structural similarity to those of adenosine-to-inosine editing enzyme 2 (ADAR2).
• Conserved residues suggest base-specific dsRNA recognition in the minor groove, similar to ADAR2.

Conclusions:

• NF90 utilizes a dsRNA-binding mechanism analogous to ADAR2.
• The sequence of the dsRNA may dictate target recognition by NF90.
• This finding provides insights into the post-transcriptional regulation of gene expression by NF90/NF45.