Abstract：
:RNAs fold into defined tertiary structures to function in critical biological processes. While quantitative models can predict RNA secondary structure stability, we are still unable to predict the thermodynamic stability of RNA tertiary structure. Here, we probe conformational preferences of diverse RNA two-way junctions to develop a predictive model for the formation of RNA tertiary structure. We quantitatively measured tertiary assembly energetics of >1,000 of RNA junctions inserted in multiple structural scaffolds to generate a "thermodynamic fingerprint" for each junction. Thermodynamic fingerprints enabled comparison of junction conformational preferences, revealing principles for how sequence influences 3-dimensional conformations. Utilizing fingerprints of junctions with known crystal structures, we generated ensembles for related junctions that predicted their thermodynamic effects on assembly formation. This work reveals sequence-structure-energetic relationships in RNA, demonstrates the capacity for diverse compensation strategies within tertiary structures, and provides a path to quantitative modeling of RNA folding energetics based on "ensemble modularity."
journal_name
Celljournal_title
Cellauthors
Denny SK,Bisaria N,Yesselman JD,Das R,Herschlag D,Greenleaf WJdoi
10.1016/j.cell.2018.05.038subject
Has Abstractpub_date
2018-07-12 00:00:00pages
377-390.e20issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(18)30650-0journal_volume
174pub_type
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