Peptidyl-prolyl isomerase Cyclophilin71 promotes SERRATE phase separation and miRNA processing in Arabidopsis.

MicroRNAs (miRNAs) play an important role in gene regulation. In Arabidopsis, mature miRNAs are processed from primary miRNA transcripts by the Dicing complex that contains Dicer-like 1 (DCL1), SERRATE (SE), and Hyponastic Leaves 1 (HYL1). The Dicing complex can form nuclear dicing bodies (D-bodies) through SE phase separation. Here, we report that Cyclophilin71 (CYP71), a peptidyl-prolyl isomerase (PPIase), positively regulates miRNA processing. We show that CYP71 directly interacts with SE and enhances its phase separation, thereby promoting the formation of D-body and increasing the activity of the Dicing complex. We further show that the PPIase activity is important for the function of CYP71 in miRNA production. Our findings reveal orchestration of miRNA processing by a cyclophilin protein and suggest the involvement of peptidyl-prolyl cis-trans isomerization, a structural mechanism, in SE phase separation and miRNA processing.

Phase separation of SERRATE drives dicing body assembly and promotes miRNA processing in Arabidopsis.

MicroRNA (miRNA) production entails the step-wise processing of primary miRNAs (pri-miRNAs) into precursor miRNAs (pre-miRNAs) and miRNA/* duplexes by Dicing complexes containing DCL1, HYL1 and SE, which are localized in nuclear dicing bodies (D-bodies)1,2. Here, we show that D-bodies are phase-separated condensates. SE forms droplets and drives DCL1, HYL1 and pri/pre-miRNAs into the droplets in vitro, and mutation of SE abrogates the formation of D-bodies in vivo, which indicates that D-bodies arise through SE-mediated phase separation. Disruption of SE phase separation greatly reduces its activity in promoting miRNA processing both in vitro and in vivo. We further show that pre-miRNAs are processed into miRNA/* duplexes in the droplets and, after processing, miRNA/* duplexes are bound by HYL1 and released from the droplets. Our findings provide evidence that efficient miRNA processing depends on the SE-phase-separation-mediated formation of D-bodies and suggest a paradigm that the products made in phase-separated condensates can be shipped out for subsequent processes.

Proliferative myositis and nodular fasciitis: a retrospective study with clinicopathologic and radiologic correlation.

Proliferative myositis (PM) and nodular fasciitis (NF) are two diseases easily misdiagnosed as cancer, often promoting unnecessary invasive procedures. To make accurate diagnoses of PM and NF and for the differential diagnosis between them, we performed a retrospective study to evaluate the roles of the clinical, radiologic, and pathologic characteristics of PM and NF. With an emphasis on the clinicopathologic and radiologic characteristics, we conducted a retrospective study of 8 cases of PM and 64 cases of NF that were diagnosed between 2012 and 2018. According to MRI findings, the lesions of PM and NF appeared as homogeneous masses with homogenous hypointensity or isointensity on T1-weighted images and as moderately or markedly hyperintense signals on T2-weighted images compared to skeletal muscle. In terms of histopathologic features, the differences between PM and NF mainly consisted of the presence of ganglion-like myofibroblasts with vesicular nuclei and basophilic cytoplasm in PM. The areas abundant in myxoid stroma with inflammatory infiltration that did not have abundant ganglion-like cells suggest NF. Immunohistochemically, the spindle-shaped cells of PM stained positive for smooth muscle actin (SMA), while the ganglion-like cells were negative. The spindle-shaped cells of NF showed diffuse expression of SMA, calponin, and vimentin. Our comprehensive study further demonstrated that PM and NF had a wide clinicopathologic and radiologic spectrum. Correlation with the clinical, radiologic and pathologic characteristics may help clinicians and pathologists make accurate diagnoses.