Biology subjects

xiao, y.

Publications and source records attributed to xiao, y..

5 recordsLinked to original sources

bioRxiv2026

The U6 snRNA capping enzyme Amus/MePCE is required for the stability of U6atac and the processing of introns with features of both major and minor classes

Over 99% of the introns in humans are removed by the major spliceosome with the U6 snRNA as the catalytic component while the rest 1% by the minor spliceosome containing U6atac. Recent evidence supports mechanistic interactions between the two splicing pathways even though they have been considered as operating in parallel. Here we report a unique genetic condition in which both splicing pathways are partially impaired, and present evidence supporting inter-pathway interactions. We recently showed that the Drosophila Amus protein and its mammalian homolog MePCE serve as the methyltransferase of U6 and protect its stability. We show here that U6atac is greatly reduced under the same amus or mepce mutant backgrounds, suggesting Amus/MePCE serves the same protective function for U6atac. Interestingly, the processing of canonical minor introns is not significantly affected in the mutants, suggesting that a minimal amount of U6atac is sufficient for those reactions. In contrast, the splicing of a second class of minor spliceosome sensitive introns are inhibited. These introns harbor splice sites different from the minor consensus even though they interact favorably with the minor spliceosome as shown by others. Interestingly, most members of this class of minor-like introns are evolutionarily younger than their canonical counterparts, and our in-depth analysis of one such intron supports that some of them might be functionally neutral. Our study provides empirical evidence supporting the existence of a class of introns jointly regulated by the two splicing pathways, and revealing additional complexity in the functional evolution of minor splicing.

genetics↗

bioRxiv2022

ATM-Mediated Translocation of RanBPM Regulates DNA Damage Response by Stabilizing p21 in Non-Small Cell Lung Cancer Cells

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-induced deaths around the world, and platinum-based chemotherapy remains a standard-of-care for most patients with advanced NSCLC. DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. In this present study, we found that the level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation, which is negatively correlated with the survival of patients. We further revealed that RanBPM protein physically interacts with p21, RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. Furthermore, RanBPM regulates DNA damage response (DDR) in a p21-dependent manner, and DNA damage promotes the translocation of RanBPM into the nucleus and regulates p21 protein stability through ATM-mediated pathways. We for the first time revealed a novel mechanism of p21 protein stability regulated by RanBPM, and the novel roles of RanBPM in the regulation of DDR.

cancer biology↗

bioRxiv2020

The effect of a novel powerful ABA mimic on the improvement of color in grapes and its mechanism

Pigment content is an important quality attribute in the grape industry, and anthocyanins are the major fruit pigments. iso-PhABA is a novel and excellent ABA analog capable of the antimetabolic inactivation of ABA. In this study, we found that iso-PhABA improved the coloration of grape berries more obviously than ABA at concentrations of 2 mg/L and 5 mg/L in two grape varieties in China. iso-PhABA treatment enhanced the anthocyanin content in the two grape varieties; specifically, the anthocyanin and delphinidin contents increased in both the Jufeng and Xiahei varieties. An enzymatic activity test showed that iso-PhABA significantly promoted four key enzyme activities catalyzing anthocyanin biosynthesis. We also determined the affinity between iso-PhABA and ABA receptors using ABA as a control. The results indicated that iso-PhABA had significantly to moderately higher affinities for some ABA receptors, including PYR1, PYL2, PYL1, PYL3 and PYL10, which resulted in higher inhibition of the PP2C HAB1 in the presence of iso-PhABA than in the presence of ABA. iso-PhABA treatment increased the content of soluble sugars and grape yield without any apparent accompanying adverse effects on the quality of the grapes.

biochemistry↗

bioRxiv2019

scCAT-seq：single-cell identification and quantification of mRNA isoforms by cost-effective short-read sequencing of cap and tail

The differences in transcription start sites (TSS) and transcription end sites (TES) among gene isoforms can affect the stability, localization, and translation efficiency of mRNA. Isoforms also allow a single gene different functions across various tissues and cells However, methods for efficient genome-wide identification and quantification of RNA isoforms in single cells are still lacking. Here, we introduce single cell Cap And Tail sequencing (scCAT-seq). In conjunction with a novel machine learning algorithm developed for TSS/TES characterization, scCAT-seq can demarcate transcript boundaries of RNA transcripts, providing an unprecedented way to identify and quantify single-cell full-length RNA isoforms based on short-read sequencing. Compared with existing long-read sequencing methods, scCAT-seq has higher efficiency with lower cost. Using scCAT-seq, we identified hundreds of previously uncharacterized full-length transcripts and thousands of alternative transcripts for known genes, quantitatively revealed cell-type specific isoforms with alternative TSSs/TESs in dorsal root ganglion (DRG) neurons, mature oocytes and ageing oocytes, and generated the first atlas of the non-human primate cornea. The approach described here can be widely adapted to other short-read or long-read methods to improve accuracy and efficiency in assessing RNA isoform dynamics among single cells.

genomics↗

bioRxiv2018

PID1 alters antilipolytic action of insulin and increases lipolysis via Inhibited the activation of AKT/PKA Pathway

PurposeThe aim was to investigate the mechanism for impaired control of lipolysis in obesity by investigating the effect of PID1 on insulin-induced activation of AKT/PKA/HSL pathway and lipolysis.\n\nMethodsFirst, PID1 expression was detected in adipose tissue and blood insulin and glycerol levels were measured in high-fat diet-induced obese rats. Next, we examined the effect of different concentrations of insulin on lipolysis and AKT/PKA/HSL pathway in 3T3-L1cells. We also investigated the role of PID1 in regulating AKT/PKA/HSL cascade and lipolysis after insulin treatment and lipofectamine over-expression.\n\nResultsPID1 expression is increased in adipose tissue from HFD rat and positive correlation with insulin levels and lipolysis. In 3T3-L1 adipocytes, we found that antilipolytic effect of insulin is mediated by AKT and AKT activated by insulin can results in phosphorylation of PKA and HSL and suppresses glycerol release. However, over-expression of PID1 counteracts insulin action as indicated by glycerol releaseand reduced level of Akt phosphorylation in accordance with a decrease in the activity of insulin-dependent PKA/HSLsignaling cascade.\n\nConclusionsAll together, these data showed that activation of PID1 in adipose tissue increases lipolysis by altering the antilipolytic action of insulin. This suggests that PID1 may constitute a new strategy to ameliorate adipocyte lipolysis and hence to improve insulin sensitivity.

cell biology↗