Abstract:In this review, we describe recent advances in the field of RNA regulatory biology and relate these advances to aging science. We introduce a new term, RNA surveillance, an RNA regulatory process that is conserved in metazoans, and describe how RNA surveillance represents molecular cross-talk between two emerging RNA regulatory systems – RNA interference and RNA editing. We discuss how RNA surveillance mechanisms influence mRNA and microRNA expression and activity during lifespan. Additionally, we summarize re… Show more
“…Moreover, certain single nucleotide polymorphisms at ADAR gene loci are associated with exceptional longevity in humans; in Caenorhabditis elegans , interactions between the RNA editing machinery and ncRNA regulatory networks are partly responsible for regulating lifespan [56, 57]. These observations link brain aging and longevity with ncRNA circuitry and implicate these relationships in determining age-related cognitive changes and disease onset.…”
Section: Life Cycles and Molecular Functions Of Non-coding Rnasmentioning
Non-coding RNAs (ncRNAs) and their associated regulatory networks are increasingly being implicated in mediating a complex repertoire of neurobiological functions. Cognitive and behavioral processes are proving to be no exception. Here, we discuss the emergence of many novel, diverse, and rapidly expanding classes and subclasses of short and long ncRNAs. We briefly review the life cycles and molecular functions of these ncRNAs. We also examine how ncRNA circuitry mediates brain development, plasticity, stress responses, and aging and highlight its potential roles in the pathophysiology of cognitive disorders, including neural developmental and age-associated neurodegenerative diseases as well as those that manifest throughout the lifespan.
“…Moreover, certain single nucleotide polymorphisms at ADAR gene loci are associated with exceptional longevity in humans; in Caenorhabditis elegans , interactions between the RNA editing machinery and ncRNA regulatory networks are partly responsible for regulating lifespan [56, 57]. These observations link brain aging and longevity with ncRNA circuitry and implicate these relationships in determining age-related cognitive changes and disease onset.…”
Section: Life Cycles and Molecular Functions Of Non-coding Rnasmentioning
Non-coding RNAs (ncRNAs) and their associated regulatory networks are increasingly being implicated in mediating a complex repertoire of neurobiological functions. Cognitive and behavioral processes are proving to be no exception. Here, we discuss the emergence of many novel, diverse, and rapidly expanding classes and subclasses of short and long ncRNAs. We briefly review the life cycles and molecular functions of these ncRNAs. We also examine how ncRNA circuitry mediates brain development, plasticity, stress responses, and aging and highlight its potential roles in the pathophysiology of cognitive disorders, including neural developmental and age-associated neurodegenerative diseases as well as those that manifest throughout the lifespan.
“…It is possible that the truncated protein that we found in our aging rats might be the one where there is loss of catalytic activity. RNA editing is compromised during aging [26]. In humans, several single nucleotide polymorphisms in the RNA editing genes ADARB1 and ADARB2 were seen in extremely old age in a US-based study on centenarians.…”
Section: Discussionmentioning
confidence: 99%
“…Mature miRNAs can also undergo ADAR-mediated editing [ 25 ]. Earlier studies have shown that RNA editing is compromised during aging [ 26 , 27 ]. There is currently not much known about how adipomiRs are regulated during aging, a knowledge of which will help understand the role of these non-coding RNAs in metabolic diseases associated with aging.…”
Adipose dysfunction with aging increases risk to insulin resistance and other chronic metabolic diseases. We previously showed functional changes in microRNAs involved in pre-adipocyte differentiation with aging resulting in adipose dysfunction. However, the mechanisms leading to this dysfunction in microRNAs in adipose tissue (adipomiRs) during aging are not well understood. We determined the longitudinal changes in expression of adipomiRs and studied their regulatory mechanisms, such as miRNA biogenesis and editing, in an aging rodent model, with Fischer344 × Brown-Norway hybrid rats at ages ranging from 3 to 30 months (male/females, n > 8). Expression of adipomiRs and their edited forms were determined by small-RNA sequencing. RT-qPCR was used to measure the mRNA expression of biogenesis and editing enzymes. Sanger sequencing was used to validate editing with aging. Differential expression of adipomiRs involved in adipocyte differentiation and insulin signaling was altered with aging. Sex- and age-specific changes in edited adipomiRs were observed. An increase in miRNA biogenesis and editing enzymes (ADARs and their splice variants) were observed with increasing age, more so in female than male rats. The adipose dysfunction observed with age is attributed to differences in editing of adipomiRs, suggesting a novel regulatory pathway in aging.
“…In depth analysis of RNA-seq data will allow the identification and study of emerging modulators of aging such as regulatory ncRNAs described in section 3.2.5 (reviewed in (Montano and Long, 2011)). Reproducibility of RNA-seq will also facilitate compilation of different studies to increase sample number and statistical significance.…”
Section: System-level Analysis Of Retinal Agingmentioning
Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of “gene” itself has become ambiguous, and the central dogma is continuously being revised and expanded. Computational biology and computational medicine are no longer intellectual domains of the chosen few. Next generation sequencing (NGS) technology, together with novel methods of pattern recognition and network analyses, has revolutionized the way we think about fundamental biological mechanisms and cellular pathways. In this review, we discuss NGS-based genome-wide approaches that can provide deeper insights into retinal development, aging and disease pathogenesis. We first focus on gene regulatory networks (GRNs) that govern the differentiation of retinal photoreceptors and modulate adaptive response during aging. Then, we discuss NGS technology in the context of retinal disease and develop a vision for therapies based on network biology. We should emphasize that basic strategies for network construction and analyses can be transported to any tissue or cell type. We believe that specific and uniform guidelines are required for generation of genome, transcriptome and epigenome data to facilitate comparative analysis and integration of multi-dimensional data sets, and for constructing networks underlying complex biological processes. As cellular homeostasis and organismal survival are dependent on gene-gene and gene-environment interactions, we believe that network-based biology will provide the foundation for deciphering disease mechanisms and discovering novel drug targets for retinal neurodegenerative diseases.
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