TRIM71 is an important RNA-binding protein in development and disease, yet its direct targets have not been investigated globally. Here we describe a number of disease and developmentally-relevant TRIM71 RNA targets such as the MBNL family, LIN28B, MDM2, and TCF7L2. We describe a new role for TRIM71 as capable of positive or negative RNA regulation depending on the RNA target. We found that TRIM71 co-precipitated with IMP1 which could explain its multiple mechanisms of RNA regulation, as IMP1 is typically thought to stabilize RNAs. Deletion of the NHL domain of TRIM71 impacted its ability to bind to RNA and RNAs bound by congenital hydrocephalus-associated point mutations in the RNA-binding NHL domain of TRIM71 clustered closely with RNAs bound by the NHL deletion mutant. Our work expands the possible mechanisms by which TRIM71 may regulate RNAs and elucidates further potential RNA targets.

TRIM71 是发育和疾病中重要的 RNA 结合蛋白，但尚未在全球范围内研究其直接靶点。在这里，我们描述了许多疾病和发育相关的 TRIM71 RNA 靶标，例如MBNL家族、LIN28B、MDM2和TCF7L2. 我们将 TRIM71 的新作用描述为能够根据 RNA 目标进行正或负 RNA 调节。我们发现 TRIM71 与 IMP1 共沉淀，这可以解释其多种 RNA 调节机制，因为 IMP1 通常被认为可以稳定 RNA。TRIM71 的 NHL 结构域的缺失影响了其与 RNA 和 RNA 结合的能力，这些 RNA 与 TRIM71 的 RNA 结合 NHL 结构域中先天性脑积水相关点突变结合的 RNA 与 NHL 缺失突变体结合的 RNA 紧密聚集。我们的工作扩展了 TRIM71 调节 RNA 的可能机制，并阐明了进一步的潜在 RNA 目标。