The emerging roles of long non-coding RNAs in polyglutamine diseases

Polyglutamine (polyQ) diseases are characterized by trinucleotide repeat amplifications within genes, thus resulting in the formation of polyQ peptides, selective neuronal degeneration and possibly death due to neurodegenerative diseases (NDDs). Long non-coding RNAs (lncRNAs), which exceed 200 nucleotides in length, have been shown to play important roles in several pathological processes of NDDs, including polyQ diseases. Some lncRNAs have been consistently identified to be specific to polyQ diseases, and circulating lncRNAs are among the most promising novel candidates in the search for non-invasive biomarkers for the diagnosis and prognosis of polyQ diseases. In this review, we describe the emerging roles of lncRNAs in polyQ diseases and provide an overview of the general biology of lncRNAs, their implications in pathophysiology and their potential roles as future biomarkers and applications for therapy.     

Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies

Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs.     

The role and mechanism of long non-coding RNAs in homologous recombination repair of radiation-induced DNA damage

DNA double-strand breaks can seriously damage the genetic information that organisms depend on for survival and reproduction. Therefore, cells require a robust DNA damage response mechanism to repair the damaged DNA. Homologous recombination (HR) allows error-free repair, which is key to maintaining genomic integrity. Long non-coding RNAs (lncRNAs) are RNA molecules that are longer than 200 nucleotides. In recent years, a number of studies have found that lncRNAs can act as regulators of gene expression and DNA damage response mechanisms, including HR repair. Moreover, they have significant effects on the occurrence, development, invasion and metastasis of tumor cells, as well as the sensitivity of tumors to radiotherapy and chemotherapy. These studies have therefore begun to expose the great potential of lncRNAs for clinical applications. In this review, we focus on the regulatory roles of lncRNAs in HR repair.     

Long non-coding RNA Mirt2 relieves lipopolysaccharide-induced injury in PC12 cells by suppressing miR-429

Journal of Physiology and Biochemistry - Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the pathogenesis of spinal cord injury (SCI). This study investigated the...     

长链非编码RNA在神经系统发育及神经性疾病中的作用

长链非编码RNA(long non-coding RNA,lncRNA)是一类转录本长度在200至数千个核苷酸序列,且不具有蛋白质编码潜能的非编码RNA。相较于研究较多的微小RNA（microRNA,miRNA）和干扰小RNA（small interfering,siRNA）等非编码小RNA,lncRNA的许多功能仍尚不清楚。但越来越多的研究发现,lncRNA可通过多种方式调控中枢神经系统发育,包括表观遗传组蛋白甲基化、转录辅因子调控、可变剪接调控等途经。而以上途经的异常均与多种人类重大疾病的发生密切相关,例如,阿尔兹海默症（Alzheimer’s disease,AD）、自闭症（autism spectrum disorder,ASD）、精神分裂症（schizophrenia,SZ）等。本文就lncRNA在表观遗传水平、转录水平、转录后水平和翻译水平上调控神经系统发育以及其在人类神经性疾病中的作用进行综述。     

Long non‐coding RNAs in non‐small cell lung cancer as biomarkers and therapeutic targets

Lung cancer‐associated mortality is the most common cause of cancer death worldwide. Non‐coding RNAs (ncRNAs), with no protein‐coding ability, have multiple biological roles. Long non‐coding RNAs (lncRNAs) are a recently characterized class of ncRNAs that are over 200 nucleotides in length. Many lncRNAs have the ability of facilitating or inhibiting the development and progression of tumours, including non‐small cell lung cancer (NSCLC). Because of their fundamental roles in regulating gene expression, along with their involvement in the biological mechanisms underlying tumourigenesis, they are a promising class of tissue‐ and/or blood‐based cancer biomarkers. In this review, we highlight the emerging roles of lncRNAs in NSCLC, and discuss their potential clinical applications as diagnostic and prognostic markers and as therapeutic targets.     

Long noncoding RNA: An emerging diagnostic and therapeutic target in kidney diseases

Long noncoding RNAs (lncRNAs) have critical roles in the development of many diseases including kidney disease. An increasing number of studies have shown that lncRNAs are involved in kidney development and that their dysregulation can result in distinct disease processes, including acute kidney injury, chronic kidney disease, and renal cell carcinoma. Understanding the roles of lncRNAs in kidney disease may provide new diagnostic and therapeutic opportunities in the clinic. This review provides an overview of lncRNA characteristics, and biological function and discusses specific studies that provide insight into the function and potential application of lncRNAs in kidney disease treatment.     

Unveiling the hidden function of long non-coding RNA by identifying its major partner-protein

Tens of thousands of long non-coding RNAs (lncRNAs) have been discovered in eukarya, but their functions are largely unknown. Fortunately, lncRNA–protein interactions may offer details of how lncRNAs play important roles in various biological processes, thus identifying proteins associated with lncRNA is critical. Here we review progress of molecular archetypes that lncRNAs execute as guides, scaffolds, or decoys for protein, focusing on advantages, shortcomings and applications of various conventional and emerging technologies to probe lncRNAs and protein interactions, including protein-centric biochemistry approaches such as nRIP and CLIP, and RNA-centric biochemistry approaches such as ChIRP, CHART and RAP. Overall, this review provides strategies for probing interactions between lncRNAs and protein.     

长非编码RNA的作用机制及在肿瘤发生发展中的意义

功能基因组学的飞速发展将越来越多的目光引向了对非编码转录产物功能的研究。在人的转录组中,存在着一类长度大于200nt,但并不具备编码蛋白质功能的基因转录产物,即长非编码RNA(long noncoding RNA,lncRNA)。相比于小分子RNA,它们仍是目前基因组转录产物中较为陌生的部分。在整个基因组转录产物中,lncRNA所占的比例远远超过编码RNA所占的比例。不同于编码RNA,lncRNA的保守性要差得多,然而在其分子内部,却含有较为保守的局部区段,且其表达具有时空特异性,这些现象都提示了lncRNA具有重要的生理生化功能。越来越多的研究表明,lncRNA在基因表达调控方面发挥着十分重要的作用,与物种进化、胚胎发育、物质代谢以及肿瘤发生等都有着紧密的联系,其功能的深入研究将使目前对细胞的结构网络和调控网络的认识带来革命性的变化,具有不可估量的科学和临床价值。该文将着重讨论lncRNA在不同层面上对基因表达的调控机制以及在肿瘤发生发展中的意义。     

Long Non-coding RNAs in the Cytoplasm

An enormous amount of long non-coding RNAs (lncRNAs) transcribed from eukaryotic genome are important regulators in different aspects of cellular events. Cytoplasm is the residence and the site of action for many lncRNAs. The cytoplasmic lncRNAs play indispensable roles with multiple molecular mechanisms in animal and human cells. In this review, we mainly talk about functions and the underlying mechanisms of lncRNAs in the cytoplasm. We highlight relatively well-studied examples of cytoplasmic lncRNAs for their roles in modulating mRNA stability, regulating mRNA translation, serving as competing endogenous RNAs, functioning as precursors of microRNAs, and mediating protein modifications. We also elaborate the perspectives of cytoplasmic lncRNA studies.     

动物长链非编码RNA研究进展

长链非编码RNA(long non-coding RNA,lncRNA)是一类广泛存在于动植物体内、长度大于200nt、基本不编码蛋白质的转录本。研究表明,lncRNA能够协助蛋白质复合体转运、参与基因和染色体的激活与失活调控等,在胚胎发育、肌肉生长、脂肪沉积以及免疫应答等过程中发挥重要作用。近年来,在人类基因组计划和ENCODE(The Encyclopedia of DNA Elements)计划推动下,在动物中不仅鉴定出数量众多的lncRNA,而且在lncRNA调控脂肪代谢、肌肉发育以及免疫抗病等重要生物学过程的机理研究方面也取得了突破性的进展。这些研究结果颠覆了lncRNA不编码蛋白的传统观念,提出了lncRNA编码功能性小肽调控生物学过程的新模型。本文主要介绍了动物lncRNA的特征与类型、常用数据库、生物学功能、分子调控模型以及未来lncRNA的研究方向,以期为动物lncRNA功能研究提供参考信息。