Brassinosteroids (BRs) are essential phytohormones that play crucial roles in plant growth and development. Perception of BRs requires an active complex of brassinosteroid-insensitive 1 (BRI1) and BRI1-associated kinase 1 (BAK1). Recognized by the extracellular leucine-rich repeat (LRR) domain of BRI1, BRs induce a phosphorylation-mediated cascade to regulate gene expression. Here we present the crystal structures of BRI1-LRR in free and brassinolide (BL)-bound forms. BRI1-LRR exists as a monomer in crystals and solution independent of BL. It comprises a helical solenoid structure that accommodates a separate insertion domain at its concave surface. Sandwiched between them, BL binds to a hydrophobicity-dominating surface groove on BRI1-LRR. BL recognition by BRI1-LRR is through an induced-fit mechanism involving stabilization of two inter-domain loops that creates a pronounced non-polar surface groove for the hormone binding. Together, our results define the molecular mechanisms by which BRI1 recognizes BRs and provide insight into BR-induced BRI1 activation.

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MicroRNAs (miRNAs), small non-coding RNAs (ncRNAs) of about 22 nucleotides in size, play important roles in gene regulation, and their dysregulation is implicated in human diseases including cancer. A variety of miRNAs could take roles in the cancer progression, participate in the process of tumor immune, and function with miRNA sponges. During the last two decades, the connection between miRNAs and various cancers has been widely researched. Based on evidence about miRNA, numerous potential cancer biomarkers for the diagnosis and prognosis have been put forward, providing a new perspective on cancer screening. Besides, there are several miRNA-based therapies among different cancers being conducted, advanced treatments such as the combination of synergistic strategies and the use of complementary miRNAs provide significant clinical benefits to cancer patients potentially. Furthermore, it is demonstrated that many miRNAs are engaged in the resistance of cancer therapies with their complex underlying regulatory mechanisms, whose comprehensive cognition can help clinicians and improve patient prognosis. With the belief that studies about miRNAs in human cancer would have great clinical implications, we attempt to summarize the current situation and potential development prospects in this review.