Noncoding RNA crosstalk in brain health and diseases.

The mammalian brain expresses several classes of noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). These ncRNAs play vital roles in regulating cellular processes by RNA/protein scaffolding, sponging and epigenetic modifications during the pathophysiological conditions, thereby controlling transcription and translation. Some of these functions are the result of crosstalk between ncRNAs to form a competitive endogenous RNA network. These intricately organized networks comprise lncRNA/miRNA, circRNA/miRNA, or lncRNA/miRNA/circRNA, leading to crosstalk between coding and ncRNAs through miRNAs. The miRNA response elements predominantly mediate the ncRNA crosstalk to buffer the miRNAs and thereby fine-tune and counterbalance the genomic changes and regulate neuronal plasticity, synaptogenesis and neuronal differentiation. The perturbed levels and interactions of the ncRNAs could lead to pathologic events like apoptosis and inflammation. Although the regulatory landscape of the ncRNA crosstalk is still evolving, some well-known examples such as lncRNA Malat1 sponging miR-145, circRNA CDR1as sponging miR-7, and lncRNA Cyrano and the circRNA CDR1as regulating miR-7, has been shown to affect brain function. The ability to manipulate these networks is crucial in determining the functional outcome of central nervous system (CNS) pathologies. The focus of this review is to highlights the interactions and crosstalk of these networks in regulating pathophysiologic CNS function.

Mehta SL ，Chokkalla AK ，Vemuganti R 《-》

A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.

Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs-a long ncRNA, a circular RNA, and two microRNAs-using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7-targeted mRNAs and enables accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as in neurons, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.

Kleaveland B ，Shi CY ，Stefano J ，Bartel DP ... -  《-》

ceRNA crosstalk mediated by ncRNAs is a novel regulatory mechanism in fish sex determination and differentiation.

Competing endogenous RNAs (ceRNAs) are vital regulators of gene networks in mammals. The involvement of noncoding RNAs (ncRNAs) as ceRNA in genotypic sex determination (GSD) and environmental sex determination (ESD) in fish is unknown. The Chinese tongue sole, which has both GSD and ESD mechanisms, was used to map the dynamic expression pattern of ncRNAs and mRNA in gonads during sex determination and differentiation. Transcript expression patterns shift during the sex differentiation phase, and ceRNA modulation occurs through crosstalk of differentially expressed long ncRNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and sex-related genes in fish. Of note was the significant up-regulation of a circRNA from the sex-determining gene dmrt1 (circular RNA dmrt1) and a lncRNA, called AMSDT (which stands for associated with male sex differentiation of tongue sole) in Chinese tongue sole testis. These two ncRNAs both share the same miRNA response elements with gsdf, which has an up-regulated expression when they bind to miRNA cse-miR-196 and concurrent down-regulated female sex-related genes to facilitate testis differentiation. This is the first demonstration in fish that ceRNA crosstalk mediated by ncRNAs modulates sexual development and unveils a novel regulatory mechanism for sex determination and differentiation.

Tang L ，Huang F ，You W ，Poetsch A ，Nóbrega RH ，Power DM ，Zhu T ，Liu K ，Wang HY ，Wang Q ，Xu X ，Feng B ，Schartl M ，Shao C ... -  《-》

Research Status of Differentially Expressed Noncoding RNAs in Type 2 Diabetes Patients.

Noncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM. The differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA-miRNA and circRNA-miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE-RAGE signaling pathways of diabetic complications. A total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE-RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE-RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications. Noncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.

Shi R ，Chen Y ，Liao Y ，Li R ，Lin C ，Xiu L ，Yu H ，Ding Y ... -  《-》

Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis.

Ilieva MS 《Cells》