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RNA language models predict mutations that improve RNA function

delete2024-12-05
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OA
AI
Y
Yekaterina Shulgina
M
Marena Trinidad
C
Conner J. Langeberg
H
Hunter Nisonoff
S
Seyone Chithrananda
P
Petr Skopintsev
A
Amos J. Nissley
J
Jaymin R. Patel
R
Ron Boger
H
Honglue Shi
P
Peter H. Yoon
E
Erin Doherty
T
Tara Pande
A
Aditya M. Iyer
J
Jennifer A. Doudna
J
J.H.D. Cate *
DOI:10.1038/s41467-024-54812-ydelete
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摘要

摘要

En 中文
Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. RNA structure prediction is not yet possible due to a lack of high-quality reference data associated with organismal phenotypes that could inform RNA function. We present GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB). GARNET links RNA sequences to experimental and predicted optimal growth temperatures of GTDB reference organisms. Using GARNET, we develop sequence- and structure-aware RNA generative models, with overlapping triplet tokenization providing optimal encoding for a GPT-like model. Leveraging hyperthermophilic RNAs in GARNET and these RNA generative models, we identify mutations in ribosomal RNA that confer increased thermostability to the Escherichia coli ribosome. The GTDB-derived data and deep learning models presented here provide a foundation for understanding the connections between RNA sequence, structure, and function.
Keyword:
EVOLUTIONARY SEQUENCE-ANALYSIS
RIBOSOMAL-RNA
PROTEIN
VISUALIZATION
ALIGNMENT
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Nature Communications
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15.7
论文数:
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被引数:
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Howard Hughes Medical Institute
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论文数: 7.8K
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U
University of California Berkeley
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论文数: 2.8W
被引数: 11.3W
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University of California System
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