{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:45:41Z","timestamp":1792140341330,"version":"4.4.0"},"reference-count":86,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100005303","name":"Boston College","doi-asserted-by":"publisher","award":["The lab startup fund to H.Z."],"award-info":[{"award-number":["The lab startup fund to H.Z."]}],"id":[{"id":"10.13039\/100005303","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM136437"],"award-info":[{"award-number":["R35GM136437"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The YTH domain was recently demonstrated as a promising tool for recognizing and regulating m6A-modified RNAs. However, the deficiency in binding affinity (micromolar range) and selectivity (off-target binding) for m6A of the wild-type YTH domain limit its sensitivity and accuracy for m6A recognition. Engineering strategies for improving the affinity and selectivity of such epitranscriptomic readers remain lacking. Here, we demonstrate that site-specific introduction of noncanonical tryptophan derivatives within the aromatic m6A-binding pocket of the YTH domain modulates the binding affinity and selectivity. Specifically, we report two YTH variants, with 5-bromotryptophan and 5-hydroxytryptophan incorporated at the W465 of the YTH domain of YTHDF1, which show improved binding affinity and selectivity against m6A-modified RNAs. DFT-based energy decomposition analysis indicates that the binding affinity can be modulated through the substitution group\u2019s effect on the dispersion force in the van der Waals recognition complex, suggesting a critical role of the CH\u2013\u03c0 interaction in m6A-reader recognition. This work reports new reader domains with improved m6A recognition and demonstrates the potential of m6A reader engineering via genetic code expansion.<\/jats:p>","DOI":"10.1021\/acschembio.6c00476","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:02:08Z","timestamp":1788980528000},"page":"2611-2621","source":"Crossref","is-referenced-by-count":0,"title":["Development of m6A Readers for Enhanced Recognition In Vitro via Genetic Code Expansion"],"prefix":"10.1021","volume":"21","author":[{"given":"Michael","family":"Addo","sequence":"first","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Ficaretta","sequence":"additional","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Chang","sequence":"additional","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Qiu","sequence":"additional","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5459-7338","authenticated-orcid":true,"given":"Chong","family":"Teng","sequence":"additional","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4967-663X","authenticated-orcid":true,"given":"Junwei Lucas","family":"Bao","sequence":"additional","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6231-5302","authenticated-orcid":true,"given":"Abhishek","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-4742","authenticated-orcid":true,"given":"Huiqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Boston College , , , ,","place":["Chestnut Hill, Massachusetts, United States, 02467"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"issue":"1","key":"2026101523062118200_cit1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/0092-8674(74)90153-6","article-title":"Existence of methylated messenger RNA in mouse L cells","volume":"1","author":"Perry","year":"1974","journal-title":"Cell"},{"issue":"10","key":"2026101523062118200_cit2","doi-asserted-by":"publisher","first-page":"3971","DOI":"10.1073\/pnas.71.10.3971","article-title":"Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells","volume":"71","author":"Desrosiers","year":"1974","journal-title":"Proc. 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