The PHYB–FOF2–VOZ2 module functions to finetune flowering in response to changes in light quality by modulating FLC expression in Arabidopsis

Proper timing of flowering under different environmental conditions is critical for plant propagation.Light quality is a pivotal environmental cue that plays a critical role in flowering regulation.Plants tend to flower late under light with a high red(R)/far-red(FR)light ratio but early under light with a low R/FR light ratio.However,how plants fine-tune flowering in response to changes in light quality is not well understood.Here,we demonstrate that F-box of Flowering 2(FOF2),an autonomous pathway–related regulator,physically interacts with VASCULAR PLANT ONE-ZINC FINGER 1 and 2(VOZ1 and VOZ2),which are direct downstream factors of the R/FR light receptor phytochrome B(PHYB).We show that PHYB physically interacts with FOF2,mediates stabilization of the FOF2 protein under FR light and end-of-day FR light,and enhances FOF2 binding to VOZ2,which leads to degradation of VOZ2 by SCF^(FOF2) E3 ligase.By contrast,PHYB mediates degradation of FOF2 protein under R light and end-of-day R light.Genetic interaction studies demonstrated that FOF2 functions downstream of PHYB to promote FLC expression and inhibit flowering under both high R/FR light and simulated shade conditions,processes that are partially dependent on VOZ proteins.Taken together,our findings suggest a novel mechanism whereby plants fine-tune flowering time through a PHYB–FOF2–VOZ2 module that modulates FLC expression in response to changes in light quality.

哺乳动物TRIM71蛋白RNA结合特性的分子机制研究

TRIM71 is an RNA-binding protein with ubiquitin ligase activity.Numerous functions of mammalian TRIM71,including cell cycle regulation,embryonic stem cell(ESC)self-renewal,and reprogramming of pluripotent stem cells,are related to its RNA-binding property.We previously reported that a long noncoding RNA(lnc RNA)Trincr1 interacts with mouse TRIM71(m TRIM71)to repress FGF/ERK pathway in mouse ESCs(m ESCs).Herein,we identify an RNA motif specifically recognized by m TRIM71 from Trincr1 RNA,and solve the crystal structure of the NHL domain of m TRIM71 complexed with the RNA motif.Similar to the zebrafish TRIM71,m TRIM71 binds to a stem-loop structured RNA fragment of Trincr1,and an adenosine base at the loop region is crucial for the m TRIM71 interaction.We map similar hairpin RNAs preferably bound by TRIM71 in the m RNA UTRs of the cell-cycle related genes regulated by TRIM71.Furthermore,we identify key residues of m TRIM71,conserved among mammalian TRIM71 proteins,required for the RNA-binding property.Single-site mutations of these residues significantly impair the binding of TRIM71 to hairpin RNAs in vitro and to m RNAs of Cdkn1a/p21 and Rbl2/p130 in m ESCs.Furthermore,congenital hydrocephalus(CH)specific mutation of m TRIM71 impair its binding to the RNA targets as well.These results reveal molecular mechanism behind the recognition of RNA by mammalian TRIM71 and provide insights into TRIM71 related diseases.

Acidic pH transiently prevents the silencing of self-renewal and dampens microRNA function in embryonic stem cells

Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells.However,little is known about its regulatory roles in gene expression and cell fate determination.Here,we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells(mESCs).Importantly,acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions.Furthermore,acidic pH partially blocks the differentiation of human ESCs(hESCs).Mechanistically,acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs.Interestingly,AGO1 protein is also downregulated by acidic pH in cancer cells.Altogether,this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells(PSCs).