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Genes for RNA-binding proteins involved in neuralspecific functions and diseases are downregulated in Rubinstein-Taybi iNeurons 被引量:2
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作者 Lidia Larizza Luciano Calzari +1 位作者 Valentina Alari Silvia Russo 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第1期5-14,共10页
Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the ... Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the neurodevelopmental Rubinstein Taybi Syndrome(RSTS)caused by mutations in the genes encoding CBP/p300 acetyltransferases.We discuss top and functionally connected downregulated genes sorted to“RNA processing”and“Ribonucleoprotein complex biogenesis”Gene Ontology clusters.The first set of downregulated RBPs includes members of hnRNHP(A1,A2B1,D,G,H2-H1,MAGOHB,PAPBC),core subunits of U small nuclear ribonucleoproteins and Serine-Arginine splicing regulators families,acting in precursor messenger RNA alternative splicing and processing.Consistent with literature findings on reduced transcript levels of serine/arginine repetitive matrix 4(SRRM4)protein,the main regulator of the neural-specific microexons splicing program upon depletion of Ep300 and Crebbp in mouse neurons,RSTS iNeurons show downregulated genes for proteins impacting this network.We link downregulated genes to neurological disorders including the new HNRNPH1-related intellectual disability syndrome with clinical overlap to RSTS.The set of downregulated genes for Ribosome biogenesis includes several components of ribosomal subunits and nucleolar proteins,such NOP58 and fibrillarin that form complexes with snoRNAs with a central role in guiding post-transcriptional modifications needed for rRNA maturation.These nucleolar proteins are“dual”players as fibrillarin is also required for epigenetic regulation of ribosomal genes and conversely NOP58-associated snoRNA levels are under the control of NOP58 interactor BMAL1,a transcriptional regulator of the circadian rhythm.Additional downregulated genes for“dual specificity”RBPs such as RUVBL1 and METTL1 highlight the links between chromatin and the RBP-ome and the contribution of perturbations in their cross-talk to RSTS.We underline the hub position of CBP/p300 in chromatin regulation,the impact of its defect on neurons’post-transcriptional regulation of gene expression and the potential use of epidrugs in therapeutics of RBP-caused neurodevelopmental disorders. 展开更多
关键词 alternative splicing CBP/p300 chromatin regulators downregulated genes induced pluripotent stem cell-neurons neurodevelopmental disorders ribosome biogenesis RNA-binding proteins RNASEQ Rubinstein-Taybi
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表观遗传调控pre-mRNA的选择性剪接 被引量:6
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作者 赵金璇 王芳 +1 位作者 徐峥嵘 范怡梅 《遗传》 CAS CSCD 北大核心 2014年第3期248-255,共8页
选择性剪接是真核生物基因表达过程中的关键环节,是蛋白质多样性的主要来源,在生物的分化、发育及疾病的发生中扮演重要角色。传统的选择性剪接调控机制的研究多集中于RNA序列元件及与之相关的一些剪接因子,但近期的突破性研究指出表观... 选择性剪接是真核生物基因表达过程中的关键环节,是蛋白质多样性的主要来源,在生物的分化、发育及疾病的发生中扮演重要角色。传统的选择性剪接调控机制的研究多集中于RNA序列元件及与之相关的一些剪接因子,但近期的突破性研究指出表观遗传因素在选择性剪接的调控中发挥重要作用。DNA甲基化、染色质结构、组蛋白修饰相互影响并作用于pre-mRNA的选择性剪接,构成一个庞大、复杂的调控网络,表明表观遗传因素不仅决定着基因转录的起始,还影响其转录本剪接的结果。文章综述了近年来pre-mRNA选择性剪接的表观遗传调控的研究进展,探讨了DNA甲基化、染色质结构、组蛋白修饰在pre-mRNA选择性剪接中的可能作用,并展望了其对人类疾病研究所带来的深远影响。 展开更多
关键词 选择性剪接 RNAⅡ型聚合酶 DNA甲基化 组蛋白修饰 染色质结构
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Regulatory mechanisms of long non-coding RNAs
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作者 Zhigang Luo 《Oncology and Translational Medicine》 2019年第3期147-151,共5页
Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still n... Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification(DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing(AS) may play a significant role in the post-transcriptional regulation of lncRNAs. 展开更多
关键词 long NON-CODING RNAs(lncRNAs) regulatory mechanisms TRANSCRIPTIONAL factors chromatin state alternative splicing RNA editing microRNA(miRNA)
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Post-transcriptional regulation of seed dormancy and germination: Current understanding and future directions 被引量:5
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作者 Rocío Soledad Tognacca Javier Francisco Botto 《Plant Communications》 2021年第4期1-22,共22页
Seed dormancy is a developmental checkpoint that prevents mature seeds from germinating under conditions that are otherwise favorable for germination.Temperature and light are themost relevant environmental factors th... Seed dormancy is a developmental checkpoint that prevents mature seeds from germinating under conditions that are otherwise favorable for germination.Temperature and light are themost relevant environmental factors that regulate seed dormancy and germination.These environmental cues can trigger molecular and physiological responses including hormone signaling,particularly that of abscisic acid and gibberellin.The balance between the content and sensitivity of these hormones is the key to the regulation of seed dormancy.Temperature and light tightly regulate the transcription of thousands of genes,as well as other aspects of gene expression such asmRNAsplicing,translation,and stability.Chromatin remodeling determines specific transcriptional outputs,and alternative splicing leads to different outcomes and produces transcripts that encode proteins with altered or lost functions.Proper regulation of chromatin remodeling and alternative splicing may be highly relevant to seed germination.Moreover,microRNAs are also critical for the control of gene expression in seeds.This review aims to discuss recent updates on post-transcriptional regulation during seed maturation,dormancy,germination,and post-germination events.We propose future prospects for understanding howdifferent post-transcriptional processes in crop seeds can contribute to the design of genotypes with better performance and higher productivity. 展开更多
关键词 alternative splicing chromatin remodeling DORMANCY GERMINATION microRNA(miRNA) SEEDS
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哺乳动物细胞mRNA剪接调控的分子机制
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作者 程呈 龚秀峰 惠静毅 《生命科学》 CSCD 北大核心 2010年第7期697-702,共6页
mRNA的可变剪接是指一个单一的mRNA前体(pre-mRNA)经过不同的剪接加工方式生成多种mRNA变异体(variants)的过程,这些变异体最终可以编码合成具有不同结构和功能的蛋白质。在过去的10多年中,大量数据表明,可变剪接是增加转录组和蛋白质... mRNA的可变剪接是指一个单一的mRNA前体(pre-mRNA)经过不同的剪接加工方式生成多种mRNA变异体(variants)的过程,这些变异体最终可以编码合成具有不同结构和功能的蛋白质。在过去的10多年中,大量数据表明,可变剪接是增加转录组和蛋白质组多样性的重要资源,也是调控哺乳动物细胞基因表达的重要步骤。可变剪接具有高度的组织与发育阶段特异性,并受到外界信号的控制。剪接调控的紊乱与疾病的发生发展密切相关。该文将对哺乳动物细胞mRNA剪接调控的分子机制进行阐述。 展开更多
关键词 mRNA剪接 剪接调控 可变剪接 信号转导 MIRNA 染色质结构
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染色质结构与mRNA可变剪接
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作者 蒋琰 惠静毅 《生命的化学》 CAS CSCD 2014年第4期449-455,共7页
mRNA的可变剪接(alternative splicing)是一种由一个mRNA前体(pre-mRNA)通过不同的剪接方式产生多个mRNA变异体(variants)的RNA加工过程。在过去很长一段时间里,人们认为mRNA剪接过程是独立于转录过程的一个转录后RNA加工过程。然而,越... mRNA的可变剪接(alternative splicing)是一种由一个mRNA前体(pre-mRNA)通过不同的剪接方式产生多个mRNA变异体(variants)的RNA加工过程。在过去很长一段时间里,人们认为mRNA剪接过程是独立于转录过程的一个转录后RNA加工过程。然而,越来越多的实验证明mRNA剪接在很大程度上是与转录偶联发生的。因此,剪接调控会受到与转录相关因素的调控。本文将对染色质与mRNA剪接调控的相关性和染色质结构调控可变剪接的分子机制进行阐述。 展开更多
关键词 mRNA剪接 剪接调控 可变剪接 染色质 核小体 组蛋白修饰 DNA甲基化
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拟南芥染色质重塑因子编码基因INO80新的可变剪切转录本
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作者 安增选 朱炎 《复旦学报(自然科学版)》 CAS CSCD 北大核心 2015年第6期742-751,共10页
可变剪切是基因转录本调控的重要方式之一,在植物中大量存在.研究表明可变剪切存在于植物不同发育阶段以及受应答环境变化的调控.INO80是一类保守的染色质重塑因子,在表观遗传学调控中发挥着重要的作用.我们在对拟南芥INO80展开功能分析... 可变剪切是基因转录本调控的重要方式之一,在植物中大量存在.研究表明可变剪切存在于植物不同发育阶段以及受应答环境变化的调控.INO80是一类保守的染色质重塑因子,在表观遗传学调控中发挥着重要的作用.我们在对拟南芥INO80展开功能分析时,意外发现了一个新的可变剪切转录本,At3G57300.3.通过定量PCR发现其表达具有一定的器官特异性,在不同条件处理时其转录水平也会发生变化.At3G57300.3编码了含有918个氨基酸的截短蛋白,在体外能够与H2A.Z-H2B结合,但缺乏完整的ATPase结构域,因而可能发挥着与全长蛋白不同的功能. 展开更多
关键词 可变剪切 染色质重塑因子 INO80 H2A.Z
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