About this Research Topic
The Encyclopedia of DNA Elements (ENCODE) project reported that three-quarters of the human genome was capable of being transcribed, of which a mere 3% was translated into proteins. This indicates that contrary to central dogma, non-coding RNAs (ncRNAs) represent most of the human transcriptome.
The importance of this non-coding transcriptome has become increasingly clear in recent years. Comparative genomic analysis has demonstrated a significant difference in genome utilization among species; e.g., the protein-coding genome constitutes almost the entire genome of unicellular yeast, but only 2% of the mammalian genome. Furthermore, the non-coding transcriptome is often dysregulated in cancer. These observations suggest that the transcriptome is of crucial importance in the greater complexity of higher eukaryotes, and in mechanisms of pathogenesis. Assigning function to non-coding sequence will, therefore, undoubtedly lead to important insight about basic physiology and disease progression.
NcRNAs are grouped to different subclasses; from short ncRNAs like miRNAs, to middle range ncRNAs like snRNAs, and lastly the long ncRNAs (lncRNAs). LncRNAs are diverse and regulate transcription, stability or translation of protein-coding genes in the mammalian genome. Natural antisense transcripts (NATs) constitute a group of lncRNAs that are transcribed from the opposite strand of protein-coding or non-protein-coding (sense) genes. NATs can form complex three-dimensional secondary structures with the capacity to bind to proteins as well as to nucleic acids. This dual capacity renders NATs an ideal regulator in protein-nucleic acid networks. Indeed, NATs are widely present in the human genome, and on average ~38% of genomic loci in cancer cells express sense/ antisense pairs. Although several NATs are shown to influence in post-transcriptional manners the expression of their sense protein-coding transcripts via cis-mediated regulation, the NATs are in general expressed in lower copy numbers (~10-100 fold) than their sense partners. At present, it is not clear how NATs modulate the post-transcriptional processing of their high copy sense transcripts. This question remains unresolved in the antisense-RNA field.
In this Research Topic, we aim to publish high quality studies investigating the mechanisms of action of lncRNAs on oncogenesis and cancer progression, with particular emphasis on how low copy NATs regulate post-transcriptional processing of their oncogenic or tumor suppressor sense transcripts. This Research Topic welcomes Original Research, Reviews, Mini Reviews and Perspectives with a focus on the post-transcriptional molecular aspects of lncRNAs, particularly NATs, which could provide new insights into their regulatory features during development and when cancers and other diseases are induced. The main themes encouraged, but not limited to, are:
• Mechanisms of action of low-copy number NATs on post-transcription regulation of sense gene expression in cis during development and when cancer is induced.
• Interaction of lncRNAs, NATs in particular, with trans-acting factors to regulate the target gene expression during development and when cancer is induced.
• Bioinformatic approaches with experimental validation to analyze RNA sequence data for the ncRNAs (small and long ncRNAs) expression regulation during development and when cancer is induced.
• Stoichiometric and other molecular approaches to investigate lncRNA-, NAT in particular, dependent competing endogenous RNA cross-regulation during development and when cancer is induced.
The importance of this non-coding transcriptome has become increasingly clear in recent years. Comparative genomic analysis has demonstrated a significant difference in genome utilization among species; e.g., the protein-coding genome constitutes almost the entire genome of unicellular yeast, but only 2% of the mammalian genome. Furthermore, the non-coding transcriptome is often dysregulated in cancer. These observations suggest that the transcriptome is of crucial importance in the greater complexity of higher eukaryotes, and in mechanisms of pathogenesis. Assigning function to non-coding sequence will, therefore, undoubtedly lead to important insight about basic physiology and disease progression.
NcRNAs are grouped to different subclasses; from short ncRNAs like miRNAs, to middle range ncRNAs like snRNAs, and lastly the long ncRNAs (lncRNAs). LncRNAs are diverse and regulate transcription, stability or translation of protein-coding genes in the mammalian genome. Natural antisense transcripts (NATs) constitute a group of lncRNAs that are transcribed from the opposite strand of protein-coding or non-protein-coding (sense) genes. NATs can form complex three-dimensional secondary structures with the capacity to bind to proteins as well as to nucleic acids. This dual capacity renders NATs an ideal regulator in protein-nucleic acid networks. Indeed, NATs are widely present in the human genome, and on average ~38% of genomic loci in cancer cells express sense/ antisense pairs. Although several NATs are shown to influence in post-transcriptional manners the expression of their sense protein-coding transcripts via cis-mediated regulation, the NATs are in general expressed in lower copy numbers (~10-100 fold) than their sense partners. At present, it is not clear how NATs modulate the post-transcriptional processing of their high copy sense transcripts. This question remains unresolved in the antisense-RNA field.
In this Research Topic, we aim to publish high quality studies investigating the mechanisms of action of lncRNAs on oncogenesis and cancer progression, with particular emphasis on how low copy NATs regulate post-transcriptional processing of their oncogenic or tumor suppressor sense transcripts. This Research Topic welcomes Original Research, Reviews, Mini Reviews and Perspectives with a focus on the post-transcriptional molecular aspects of lncRNAs, particularly NATs, which could provide new insights into their regulatory features during development and when cancers and other diseases are induced. The main themes encouraged, but not limited to, are:
• Mechanisms of action of low-copy number NATs on post-transcription regulation of sense gene expression in cis during development and when cancer is induced.
• Interaction of lncRNAs, NATs in particular, with trans-acting factors to regulate the target gene expression during development and when cancer is induced.
• Bioinformatic approaches with experimental validation to analyze RNA sequence data for the ncRNAs (small and long ncRNAs) expression regulation during development and when cancer is induced.
• Stoichiometric and other molecular approaches to investigate lncRNA-, NAT in particular, dependent competing endogenous RNA cross-regulation during development and when cancer is induced.
Keywords: Natural antisense transcripts, long non-coding RNA, post-transcriptional regulation, cancer, development
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