Abstract
This review aims to summarize the current knowledge on how lncRNAs are influencing aging and cancer metabolism. Recent research has shown that senescent cells re-enter cell-cycle depending on intrinsic or extrinsic factors, thus restoring tissue homeostasis in response to age-related diseases (ARDs). Furthermore, maintaining proteostasis or cellular protein homeostasis requires a correct quality control (QC) of protein synthesis, folding, conformational stability, and degradation. Long non-coding RNAs (lncRNAs), transcripts longer than 200 nucleotides, regulate gene expression through RNA-binding protein (RBP) interaction. Their association is linked to aging, an event of proteostasis collapse. The current review examines approaches that lead to recognition of senescence-associated lncRNAs, current methodologies, potential challenges that arise from studying these molecules, and their crucial implications in clinical practice.
Highlights
Age-associated diseases such as cancer, cardiovascular diseases, obesity, neurodegenerative disorders, sarcopenia and several other conditions are dictated by distinct adjustments of gene expression programs that underlie aging
Proteostasis network control in aging regulators avoiding age-associated proteinopathies included in age-related diseases (ARDs) [4]. These mechanisms are governed by proteins that bind RNA, DNA, as well as a diversity of long non-coding RNAs, long nuclear RNAs greater than 200 nucleotides, and microRNAs, small noncoding RNA molecules with a length of 20-25 nucleotides that are involved in controlling target gene translation and post-transcriptional modulation of gene expression
We summarize proteostasis-related long non-coding RNAs (lncRNAs) associated with protein turnover, trafficking and autophagy (Table 1)
Summary
LncRNAs are heterogeneous transcripts that are not translated into proteins or encoding for small proteins [9, 21] They can be intergenic transcripts or large intergenic non-coding RNAs (lincRNAs), enhancer RNAs (eRNAs), or sense or antisense RNAs from the same or the opposite strand of mRNA that overlaps other genes. Competing endogenous RNAs (abbreviated ceRNAs), which manage RNA transcripts by competing for shared miRNAs, and circRNAs are stable and accumulate in great numbers [2, 25]. These lncRNAs have crucial roles in gene regulation, affecting different aspects of cellular homeostasis such as proliferation, migration or genomic stability by assembling transcriptional modulators, by base-pairing with mRNAs, by enrolling chromatin. The non-coding transcriptome could reveal unexpected molecular activities, offering a great potential to distinguish between normal and disease states [24]
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