Back

Short 5' UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex

Glasner, D. R.; Todd, C.; Cook, B.; D'Urso, A.; Khosla, S.; Estrada, E.; Wagner, J. D.; Bartels, M. D.; Ford, P.; Prych, J.; Hatch, K.; Yee, B. A.; Ego, K. M.; Liang, Q.; Holland, S. R.; Case, J. B.; Corbett, K. D.; Diamond, M. S.; Yeo, G. W.; Herzik, M. A.; Van Nostrand, E. L.; Daugherty, M. D.

2025-02-11 microbiology
10.1101/2025.02.11.637299 bioRxiv
Show abstract

Recognition of "non-self" nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5 cap structures, is critical for the innate immune response to viruses. Here, we demonstrate that short 5 untranslated regions (UTRs), a characteristic of many viral mRNAs, can also serve as a molecular pattern for innate immune recognition via the interferon-induced proteins IFIT2 and IFIT3. The IFIT2-IFIT3 heterodimer, formed through an intricate domain swap structure resolved by cryo-EM, mediates viral mRNA 5 end recognition, translation inhibition, and ultimately antiviral activity. Critically, 5 UTR lengths <50 nucleotides are necessary and sufficient to sensitize an mRNA to translation inhibition by the IFIT2-IFIT3 complex. Accordingly, diverse viruses whose mRNAs contain short 5 UTRs, such as vesicular stomatitis virus and parainfluenza virus 3, are sensitive to IFIT2-IFIT3-mediated antiviral activity. Our work thus reveals a pattern of antiviral nucleic acid immune recognition that takes advantage of the inherent constraints on viral genome size.

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

1
Nature Communications
○ 5641 papers in training set
Top 3%
30.4%
Similar papers in this journal
2
Nature
○ 645 papers in training set
Top 1%
11.6%
Similar papers in this journal
3
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 4%
9.4%
Similar papers in this journal
50% of probability mass above
4
Science Advances
● 1243 papers in training set
Top 4%
6.1%
Similar papers in this journal
5
Nature Microbiology
○ 155 papers in training set
Top 0.6%
5.4%
6
eLife
● 5828 papers in training set
Top 23%
5.4%
Similar papers in this journal
7
Cell Reports
○ 1498 papers in training set
Top 12%
3.2%
8
Nature Structural & Molecular Biology
236 papers in training set
Top 2%
2.7%
9
Cell
○ 431 papers in training set
Top 4%
2.6%
10
Cell Host & Microbe
126 papers in training set
Top 1%
1.8%
11
mBio
● 833 papers in training set
Top 8%
1.7%
12
Cell Research
○ 51 papers in training set
Top 0.7%
1.4%
13
Nucleic Acids Research
◐ 1281 papers in training set
Top 10%
1.3%
14
PLOS Pathogens
● 820 papers in training set
Top 8%
1.1%
15
EMBO Reports
○ 263 papers in training set
Top 5%
1.1%
16
Molecular Cell
○ 350 papers in training set
Top 4%
1.1%
17
Communications Biology
○ 993 papers in training set
Top 23%
1.1%
18
Nature Methods
○ 385 papers in training set
Top 6%
1.0%
19
PLOS Biology
● 486 papers in training set
Top 12%
0.8%
20
Science
● 477 papers in training set
Top 9%
0.8%
21
The EMBO Journal
○ 309 papers in training set
Top 7%
0.8%
22
Nature Ecology & Evolution
131 papers in training set
Top 2%
0.8%
23
Cell Systems
○ 201 papers in training set
Top 5%
0.8%
24
Journal of Experimental Medicine
● 119 papers in training set
Top 4%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.