Long non-coding RNA Databases in Cardiovascular Research

With the rising interest in the regulatory functions of long non-coding RNAs (lncRNAs) in complex human diseases such as cardiovascular diseases, there is an increasing need in public databases offering comprehensive and integrative data for all aspects of these versatile molecules. Recently, a variety of public data repositories that specialized in lncRNAs have been developed, which make use of huge high-throughput data particularly from next-generation sequencing (NGS) approaches. Here, we provide an overview of current lncRNA databases covering basic and functional annotation, lncRNA expression and regulation, interactions with other biomole-cules, and genomic variants influencing the structure and function of lncRNAs. The prominent lncRNA antisense noncoding RNA in the INK4 locus (ANRIL), which has been unequivocally associated with coronary artery disease through genome-wide association studies (GWAS), serves as an example to demonstrate the features of each individual database.     

Chromatin Isolation by RNA Purification (ChIRP)

Long noncoding RNAs are key regulators of chromatin states for important biological processes such as dosage compensation, imprinting, and developmental gene expression ^{1,2,3,4,5,6,7}. The recent discovery of thousands of lncRNAs in association with specific chromatin modification complexes, such as Polycomb Repressive Complex 2 (PRC2) that mediates histone H3 lysine 27 trimethylation (H3K27me3), suggests broad roles for numerous lncRNAs in managing chromatin states in a gene-specific fashion ^8,9. While some lncRNAs are thought to work in cis on neighboring genes, other lncRNAs work in trans to regulate distantly located genes. For instance, Drosophila lncRNAs roX1 and roX2 bind numerous regions on the X chromosome of male cells, and are critical for dosage compensation ^10,11. However, the exact locations of their binding sites are not known at high resolution. Similarly, human lncRNA HOTAIR can affect PRC2 occupancy on hundreds of genes genome-wide ^3,12,13, but how specificity is achieved is unclear. LncRNAs can also serve as modular scaffolds to recruit the assembly of multiple protein complexes. The classic trans-acting RNA scaffold is the TERC RNA that serves as the template and scaffold for the telomerase complex ¹⁴; HOTAIR can also serve as a scaffold for PRC2 and a H3K4 demethylase complex ¹³.Prior studies mapping RNA occupancy at chromatin have revealed substantial insights ^15,16, but only at a single gene locus at a time. The occupancy sites of most lncRNAs are not known, and the roles of lncRNAs in chromatin regulation have been mostly inferred from the indirect effects of lncRNA perturbation. Just as chromatin immunoprecipitation followed by microarray or deep sequencing (ChIP-chip or ChIP-seq, respectively) has greatly improved our understanding of protein-DNA interactions on a genomic scale, here we illustrate a recently published strategy to map long RNA occupancy genome-wide at high resolution ¹⁷. This method, Chromatin Isolation by RNA Purification (ChIRP) (Figure 1), is based on affinity capture of target lncRNA:chromatin complex by tiling antisense-oligos, which then generates a map of genomic binding sites at a resolution of several hundred bases with high sensitivity and low background. ChIRP is applicable to many lncRNAs because the design of affinity-probes is straightforward given the RNA sequence and requires no knowledge of the RNA''s structure or functional domains.     

长链非编码RNA数据库资源

长链非编码RNA（long non coding RNA, lncRNA)在多个水平参与调节机体的各项基础生物进程,其功能紊乱常伴随疾病的发生。鉴定lncRNA的生物学功能已成为近年来的研究热点。然而,目前从各种真核生物高通量测序中鉴定的几十万个lncRNA中,只有极少数的功能已被实验验证,这对于该领域的深入研究是个巨大的挑战。因此,许多科研机构都建立了lncRNA数据库,并且持续周期性更新,这为研究者共享、注释和分析lncRNA功能提供了十分有效的工具。本文从lncRNA原始资源整合、筛选、鉴定及功能分析和lncRNA与人类疾病等4个方面介绍各lncRNA数据库资源的最新特征和应用范围。这为研究者在选择不同数据库资源进行lncRNA鉴定和分析时提供参考。     

长链非编码RNA顺式调节作用机制的研究进展

长链非编码RNA (long non-coding RNA, lncRNA)种类众多,生物学功能复杂,与不同的分子相互作用,实现其特有的基因调控功能。可参与细胞核染色质结构的调控、m RNA的转录及转录后的加工运输、蛋白质的翻译等过程。此外,lncRNAs在邻近基因或靶基因的顺式调节机制中也发挥了重要作用,本综述主要对近年来lncRNAs通过顺式调节作用影响基因表达的机制进行综述。     

Active and repressive chromatin are interspersed without spreading in an imprinted gene cluster in the mammalian genome

The Igf2r imprinted cluster is an epigenetic silencing model in which expression of a ncRNA silences multiple genes in cis. Here, we map a 250 kb region in mouse embryonic fibroblast cells to show that histone modifications associated with expressed and silent genes are mutually exclusive and localized to discrete regions. Expressed genes were modified at promoter regions by H3K4me3 + H3K4me2 + H3K9Ac and on putative regulatory elements flanking active promoters by H3K4me2 + H3K9Ac. Silent genes showed two types of nonoverlapping profile. One type spread over large domains of tissue-specific silent genes and contained H3K27me3 alone. A second type formed localized foci on silent imprinted gene promoters and a nonexpressed pseudogene and contained H3K9me3 + H4K20me3 +/- HP1. Thus, mammalian chromosome arms contain active chromatin interspersed with repressive chromatin resembling the type of heterochromatin previously considered a feature of centromeres, telomeres, and the inactive X chromosome.