Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants
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Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants. / Theisen, Frederik Friis; Prestel, Andreas; Elkjær, Steffie; Leurs, Yannick H.A.; Morffy, Nicholas; Strader, Lucia C.; O’Shea, Charlotte; Teilum, Kaare; Kragelund, Birthe B.; Skriver, Karen.
In: Nature Communications, Vol. 15, No. 1, 592, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants
AU - Theisen, Frederik Friis
AU - Prestel, Andreas
AU - Elkjær, Steffie
AU - Leurs, Yannick H.A.
AU - Morffy, Nicholas
AU - Strader, Lucia C.
AU - O’Shea, Charlotte
AU - Teilum, Kaare
AU - Kragelund, Birthe B.
AU - Skriver, Karen
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024
Y1 - 2024
N2 - The Arabidopsis thaliana DREB2A transcription factor interacts with the negative regulator RCD1 and the ACID domain of subunit 25 of the transcriptional co-regulator mediator (Med25) to integrate stress signals for gene expression, with elusive molecular interplay. Using biophysical and structural analyses together with high-throughput screening, we reveal a bivalent binding switch in DREB2A containing an ACID-binding motif (ABS) and the known RCD1-binding motif (RIM). The RIM is lacking in a stress-induced DREB2A splice variant with retained transcriptional activity. ABS and RIM bind to separate sites on Med25-ACID, and NMR analyses show a structurally heterogeneous complex deriving from a DREB2A-ABS proline residue populating cis- and trans-isomers with remote impact on the RIM. The cis-isomer stabilizes an α-helix, while the trans-isomer may introduce energetic frustration facilitating rapid exchange between activators and repressors. Thus, DREB2A uses a post-transcriptionally and post-translationally modulated switch for transcriptional regulation.
AB - The Arabidopsis thaliana DREB2A transcription factor interacts with the negative regulator RCD1 and the ACID domain of subunit 25 of the transcriptional co-regulator mediator (Med25) to integrate stress signals for gene expression, with elusive molecular interplay. Using biophysical and structural analyses together with high-throughput screening, we reveal a bivalent binding switch in DREB2A containing an ACID-binding motif (ABS) and the known RCD1-binding motif (RIM). The RIM is lacking in a stress-induced DREB2A splice variant with retained transcriptional activity. ABS and RIM bind to separate sites on Med25-ACID, and NMR analyses show a structurally heterogeneous complex deriving from a DREB2A-ABS proline residue populating cis- and trans-isomers with remote impact on the RIM. The cis-isomer stabilizes an α-helix, while the trans-isomer may introduce energetic frustration facilitating rapid exchange between activators and repressors. Thus, DREB2A uses a post-transcriptionally and post-translationally modulated switch for transcriptional regulation.
U2 - 10.1038/s41467-024-44859-2
DO - 10.1038/s41467-024-44859-2
M3 - Journal article
C2 - 38238333
AN - SCOPUS:85182634093
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 592
ER -
ID: 381059019