RNA has important and diverse biological roles, but the molecular methods to manipulate it spatiotemporally are limited. Here, an engineered photoactivatable RNA N⁶‐methyladenosine (m⁶A) editing system with CRISPR‐Cas13 is designed to direct specific m⁶A editing. Light‐inducible heterodimerizing proteins CIBN and CRY2PHR are fused to catalytically inactive PguCas13 (dCas13) and m⁶A effectors, respectively. This system, referred to as PAMEC, enables the spatiotemporal control of m⁶A editing in response to blue light. Further optimization of this system to create a highly efficient version, known as PAMEC^R, allows the manipulation of multiple genes robustly and simultaneously. When coupled with an upconversion nanoparticle film, the optogenetic operation window is extended from the visible range to tissue‐penetrable near‐infrared wavelengths, which offers an appealing avenue to remotely control RNA editing. These results show that PAMEC is a promising optogenetic platform for flexible and efficient targeting of RNA, with broad applicability for epitranscriptome engineering, imaging, and future therapeutic development.

中文翻译：

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用CRISPR-Cas13编辑光激活RNA N6-甲基腺苷。

RNA具有重要而多样的生物学作用，但是时空操纵它的分子方法是有限的。在这里，设计了带有CRISPR‐Cas13的光激活RNA N ^6-甲基腺苷（m ⁶ A）编辑系统，旨在指导特定的m ⁶ A编辑。光诱导异源二聚体蛋白CIBN和CRY2PHR分别与催化失活的PguCas13（dCas13）和m ⁶ A效应子融合。该系统称为PAMEC，可响应蓝光对m ⁶ A编辑进行时空控制。对该系统进行进一步优化以创建一个高效的版本，称为PAMEC ^R，允许同时稳定地操纵多个基因。当与上转换纳米颗粒薄膜结合时，光遗传学操作窗口从可见光范围扩展到组织可穿透的近红外波长，这为远程控制RNA编辑提供了诱人的途径。这些结果表明，PAMEC是一种有前途的光遗传学平台，可灵活，高效地靶向RNA，在表观转录组工程，成像和未来治疗开发中具有广泛的适用性。