Long noncoding RNAs: Functional surprises from the RNA world

Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Genes & development (Impact Factor: 10.8). 08/2009; 23(13):1494-504. DOI: 10.1101/gad.1800909
Source: PubMed


Most of the eukaryotic genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs with little or no protein-coding capacity. Although the vast majority of long noncoding RNAs have yet to be characterized thoroughly, many of these transcripts are unlikely to represent transcriptional "noise" as a significant number have been shown to exhibit cell type-specific expression, localization to subcellular compartments, and association with human diseases. Here, we highlight recent efforts that have identified a myriad of molecular functions for long noncoding RNAs. In some cases, it appears that simply the act of noncoding RNA transcription is sufficient to positively or negatively affect the expression of nearby genes. However, in many cases, the long noncoding RNAs themselves serve key regulatory roles that were assumed previously to be reserved for proteins, such as regulating the activity or localization of proteins and serving as organizational frameworks of subcellular structures. In addition, many long noncoding RNAs are processed to yield small RNAs or, conversely, modulate how other RNAs are processed. It is thus becoming increasingly clear that long noncoding RNAs can function via numerous paradigms and are key regulatory molecules in the cell.

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Available from: Jeremy E Wilusz, Jun 09, 2015
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    • "Moreover, subspecies of lncRNAs have also been categorized and characterized in human[1,4], zebrafish[5], and Caenorhabditis ele- gans[6]. Recent reports have shown that similar to mRNA, lncRNA is functional and spatiotemporally expressed in tissues789. Researchers have identified several functional lncRNAs associated with skin biology such as ANCR, TINCR, U1 RNA, PRINS, BANCR, and SPRY4-IT1[10]. "
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    ABSTRACT: Background: Long noncoding RNAs (lncRNAs) play roles in almost all biological processes; however, their function and profile in skin development and pigmentation is less understood. In addition, because lncRNAs are species-specific, their function in goats has not been established. Result: We systematically identified lncRNAs in 100-day-old fetal skin by deep RNA-sequencing using the Youzhou dark goat (dark skin) and Yudong white goat (white skin) as a model of skin pigmentation. A total of 841,895,634 clean reads were obtained from six libraries (samples). We identified 1336 specific lncRNAs in fetal skin that belonged to three subtypes, including 999 intergenic lncRNAs (lincRNAs), 218 anti-sense lncRNAs, and 119 intronic lncRNAs. Our results demonstrated significant differences in gene architecture and expression among the three lncRNA subtypes, particularly in terms of density and position bias of transpose elements near the transcription start site. We also investigated the impact of lncRNAs on its target genes in cis and trans, indicating that these lncRNAs have a strict tissue specificity and functional conservation during skin development and pigmentation. Conclusion: The present study provides a resource for lncRNA studies in diseases involved in pigmentation and skin development. It expands our knowledge about lncRNA biology as well as contributes to the annotation of the goat genome.
    Preview · Article · Dec 2016 · BMC Genomics
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    • "Although these changes in gene expression are informative, further gene identifications are still required to elucidate the molecular mechanism of cataract formation. LncRNAs are identified as non-coding RNA molecules greater than 200 nucleotides in length[9,10]. They regulate gene expression in diverse biological processes. "
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    ABSTRACT: Age-related cataract is among the most common chronic disorders of ageing and is the world's leading blinding disorder. Long non-coding RNAs play important roles in several biological processes and complicated diseases. However, the role of lncRNAs in the setting of cataract is still unknown. Here, we extracted total RNAs from the transparent and age-matched cataractous human lenses, and determined lncRNA expression profiles using microarray analysis. We found that 38 lncRNAs were differentially expressed between transparent and cataractous lenses. 17 of 20 differentially expressed lncRNAs were further verified by quantitative RT-PCRs. One top abundant lncRNA, MIAT, was specifically up-regulated both in the plasma fraction of whole blood and aqueous humor of cataract patients. MIAT knockdown could affect the proliferation, apoptosis and migration of Human lens epithelial cells (HLECs) upon oxidative stress. Posterior capsule opacification (PCO) is a common complication of cataract surgery, which is associated with abnormal production of inflammatory factors. MIAT knockdown could repress tumour necrosis factor-α-induced abnormal proliferation and migration of HLECs, suggesting a potential role of MIAT in PCO-related pathological process. Moreover, we found that MIAT acted as a ceRNA, and formed a feedback loop with Akt and miR-150-5p to regulate HLEC function. Collectively, this study provides a novel insight into the pathogenesis of age-related cataract.
    Preview · Article · Jan 2016 · Journal of Cellular and Molecular Medicine
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    • "lncRNAs may belong to one or more of the following five broad categories: sense, antisense, bidirectional, intronic, or intergenic[6]. lncRNA is a major component of epigenetic regulatory networks[7]. Additionally, lncRNA expression is dysregulated in GC tissues[8]. "
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    ABSTRACT: Long noncoding RNAs (lncRNAs) play important regulatory roles in several human cancers. Integrated analysis revealed that expression of long intergenic non-coding RNA 152 (LINC00152) was significantly upregulated in gastric cancer (GC). Further analysis in a cohort of 97 GC patients revealed that LINC00152 expression was positively correlated with tumor invasion depth, lymph node metastasis, higher TNM stage, and poor survival. Gene set enrichment analysis revealed that cell proliferation and cell cycle progression were increased in patients with high LINC00152 expression. In both GC cell lines and xenograft systems, LINC00152 overexpression facilitated GC cell proliferation by accelerating the cell cycle, whereas LINC00152 knockdown had the opposite effect. Moreover, by binding to enhancer of zeste homolog 2 (EZH2), LINC00152 promotes GC tumor cell cycle progression by silencing the expression of p15 and p21. These findings suggest that LINC00152 may play contribute to the progression of GC and may be an effective therapeutic target.
    Preview · Article · Jan 2016 · Oncotarget
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