Long non‐coding RNAs in development and disease: conservation to mechanisms

Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein‐coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other...

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Published in:The Journal of pathology Vol. 250; no. 5; pp. 480 - 495
Main Authors: Tsagakis, Ioannis, Douka, Katerina, Birds, Isabel, Aspden, Julie L
Format: Journal Article
Language:English
Published: Chichester, UK John Wiley & Sons, Ltd 01.04.2020
Wiley Subscription Services, Inc
Subjects:
Animals
anti‐sense lncRNAs
Base Sequence - genetics
cancer
Cell Nucleus - genetics
conservation
Cytoplasm
Cytoplasm - metabolism
development
diabetes
Evolutionary conservation
Genomes
Humans
Invited Review
Invited Reviews
long intergenic non‐coding RNA
long non‐coding RNA
neurodegenerative disease
Neurodegenerative Diseases - genetics
Non-coding RNA
Nucleotide sequence
Proteins - genetics
RNA, Long Noncoding - genetics
stem cells
translation
United Kingdom
X chromosome inactivation
United Kingdom
long intergenic non-coding RNA
stem cells
conservation
development
anti-sense lncRNAs
neurodegenerative disease
X chromosome inactivation
translation
cancer
long non-coding RNA
diabetes
ISSN:0022-3417, 1096-9896, 1096-9896
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Abstract Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein‐coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other 95% is referred to as the ‘dark matter’ of our genomes, our understanding of which is extremely limited. Part of this ‘dark matter’ includes regions that give rise to RNAs that do not code for proteins. A subset of these non‐coding RNAs are long non‐coding RNAs (lncRNAs), which in particular are beginning to be dissected and their importance to human health revealed. To improve our understanding and treatment of disease it is vital that we understand the molecular and cellular function of lncRNAs, and how their misregulation can contribute to disease. It is not yet clear what proportion of lncRNAs is actually functional; conservation during evolution is being used to understand the biological importance of lncRNA. Here, we present key themes within the field of lncRNAs, emphasising the importance of their roles in both the nucleus and the cytoplasm of cells, as well as patterns in their modes of action. We discuss their potential functions in development and disease using examples where we have the greatest understanding. Finally, we emphasise why lncRNAs can serve as biomarkers and discuss their emerging potential for therapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
AbstractList Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein‐coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other 95% is referred to as the ‘dark matter’ of our genomes, our understanding of which is extremely limited. Part of this ‘dark matter’ includes regions that give rise to RNAs that do not code for proteins. A subset of these non‐coding RNAs are long non‐coding RNAs (lncRNAs), which in particular are beginning to be dissected and their importance to human health revealed. To improve our understanding and treatment of disease it is vital that we understand the molecular and cellular function of lncRNAs, and how their misregulation can contribute to disease. It is not yet clear what proportion of lncRNAs is actually functional; conservation during evolution is being used to understand the biological importance of lncRNA. Here, we present key themes within the field of lncRNAs, emphasising the importance of their roles in both the nucleus and the cytoplasm of cells, as well as patterns in their modes of action. We discuss their potential functions in development and disease using examples where we have the greatest understanding. Finally, we emphasise why lncRNAs can serve as biomarkers and discuss their emerging potential for therapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein-coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other 95% is referred to as the 'dark matter' of our genomes, our understanding of which is extremely limited. Part of this 'dark matter' includes regions that give rise to RNAs that do not code for proteins. A subset of these non-coding RNAs are long non-coding RNAs (lncRNAs), which in particular are beginning to be dissected and their importance to human health revealed. To improve our understanding and treatment of disease it is vital that we understand the molecular and cellular function of lncRNAs, and how their misregulation can contribute to disease. It is not yet clear what proportion of lncRNAs is actually functional; conservation during evolution is being used to understand the biological importance of lncRNA. Here, we present key themes within the field of lncRNAs, emphasising the importance of their roles in both the nucleus and the cytoplasm of cells, as well as patterns in their modes of action. We discuss their potential functions in development and disease using examples where we have the greatest understanding. Finally, we emphasise why lncRNAs can serve as biomarkers and discuss their emerging potential for therapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein-coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other 95% is referred to as the 'dark matter' of our genomes, our understanding of which is extremely limited. Part of this 'dark matter' includes regions that give rise to RNAs that do not code for proteins. A subset of these non-coding RNAs are long non-coding RNAs (lncRNAs), which in particular are beginning to be dissected and their importance to human health revealed. To improve our understanding and treatment of disease it is vital that we understand the molecular and cellular function of lncRNAs, and how their misregulation can contribute to disease. It is not yet clear what proportion of lncRNAs is actually functional; conservation during evolution is being used to understand the biological importance of lncRNA. Here, we present key themes within the field of lncRNAs, emphasising the importance of their roles in both the nucleus and the cytoplasm of cells, as well as patterns in their modes of action. We discuss their potential functions in development and disease using examples where we have the greatest understanding. Finally, we emphasise why lncRNAs can serve as biomarkers and discuss their emerging potential for therapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Author Douka, Katerina
Birds, Isabel
Aspden, Julie L
Tsagakis, Ioannis
AuthorAffiliation 1 School of Molecular and Cellular Biology, Faculty of Biological Sciences University of Leeds Leeds UK
2 LeedsOmics University of Leeds Leeds UK
AuthorAffiliation_xml – name: 1 School of Molecular and Cellular Biology, Faculty of Biological Sciences University of Leeds Leeds UK
– name: 2 LeedsOmics University of Leeds Leeds UK
Author_xml – sequence: 1
  givenname: Ioannis
  surname: Tsagakis
  fullname: Tsagakis, Ioannis
  organization: University of Leeds
– sequence: 2
  givenname: Katerina
  orcidid: 0000-0002-7126-5212
  surname: Douka
  fullname: Douka, Katerina
  organization: University of Leeds
– sequence: 3
  givenname: Isabel
  orcidid: 0000-0001-8173-3879
  surname: Birds
  fullname: Birds, Isabel
  organization: University of Leeds
– sequence: 4
  givenname: Julie L
  orcidid: 0000-0002-8537-6204
  surname: Aspden
  fullname: Aspden, Julie L
  email: j.aspden@leeds.ac.uk
  organization: University of Leeds
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32100288$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2020 The Authors. published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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ISSN 0022-3417
1096-9896
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Issue 5
Keywords long intergenic non-coding RNA
stem cells
conservation
development
anti-sense lncRNAs
neurodegenerative disease
X chromosome inactivation
translation
cancer
long non-coding RNA
diabetes
Language English
License Attribution
2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ObjectType-Review-3
content type line 23
No conflicts of interest were declared.
Equal first author.
ORCID 0000-0002-7126-5212
0000-0001-8173-3879
0000-0002-8537-6204
OpenAccessLink https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fpath.5405
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Snippet Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed...
Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed...
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StartPage 480
SubjectTerms Animals
anti‐sense lncRNAs
Base Sequence - genetics
cancer
Cell Nucleus - genetics
conservation
Cytoplasm
Cytoplasm - metabolism
development
diabetes
Evolutionary conservation
Genomes
Humans
Invited Review
Invited Reviews
long intergenic non‐coding RNA
long non‐coding RNA
neurodegenerative disease
Neurodegenerative Diseases - genetics
Non-coding RNA
Nucleotide sequence
Proteins - genetics
RNA, Long Noncoding - genetics
stem cells
translation
United Kingdom
X chromosome inactivation
Title Long non‐coding RNAs in development and disease: conservation to mechanisms
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fpath.5405
https://www.ncbi.nlm.nih.gov/pubmed/32100288
https://www.proquest.com/docview/2395446193
https://www.proquest.com/docview/2365203404
https://pubmed.ncbi.nlm.nih.gov/PMC8638664
Volume 250
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