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Article ; Online: A call to action: Improving urban green spaces to reduce health inequalities exacerbated by COVID-19.

Geary, Rebecca S / Wheeler, Benedict / Lovell, Rebecca / Jepson, Ruth / Hunter, Ruth / Rodgers, Sarah

2021 Volume 145, Page(s) 106425

Abstract: Health is not equally distributed across society; there are avoidable, unfair, systematic differences in health between population groups. Some of these same groups (older people, BAME communities, those with some non-communicable diseases (NCDs)) may be ...

Abstract	Health is not equally distributed across society; there are avoidable, unfair, systematic differences in health between population groups. Some of these same groups (older people, BAME communities, those with some non-communicable diseases (NCDs)) may be particularly vulnerable to risk of exposure and severe COVID-19 outcomes due to co-morbidities, structural vulnerabilities, and public-facing or health and social care jobs among other factors. Additionally, some of the restrictions designed to reduce SARS-CoV-2 spread impact specifically on these same groups by limiting their activity and access to preventive or health promotion services. Greenspaces, accessed with social distancing, may mitigate some of the predicted negative health effects of COVID-19 restrictions. Maintaining or increasing publicly accessible urban greenspaces, particularly for marginalised groups, is reflected in the Sustainable Development Goals, and its importance amplified in the COVID-19 pandemic. Urban greenspaces should be considered a public health and social investment and a chance to rebalance our relationship with nature to protect against future pandemics. By investing in urban public greenspaces, additional benefits (job/food creation, biodiversity promotion, carbon sequestration) may coincide with health benefits. Realising these requires a shift in the balance of decision making to place weight on protecting, enhancing and providing more appropriate greenspaces designed with local communities. The current pandemic is a reminder that humanity placing too many pressures on nature has damaging consequences. COVID-19 economic recovery programs present an opportunity for sustainable transformation if they can be leveraged to simultaneously protect and restore nature and tackle climate change and health inequalities.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; COVID-19/prevention & control ; COVID-19/psychology ; Female ; Health Status Disparities ; Humans ; Male ; Middle Aged ; Pandemics/prevention & control ; Parks, Recreational/statistics & numerical data ; Parks, Recreational/supply & distribution ; Risk Factors ; SARS-CoV-2 ; Social Environment
Language	English
Publishing date	2021-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	184600-0
ISSN	1096-0260 ; 0091-7435
ISSN (online)	1096-0260
ISSN	0091-7435
DOI	10.1016/j.ypmed.2021.106425
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Article ; Online: Drum training induces long-term plasticity in the cerebellum and connected cortical thickness.

Bruchhage, Muriel M K / Amad, Ali / Draper, Stephen B / Seidman, Jade / Lacerda, Luis / Laguna, Pedro Luque / Lowry, Ruth G / Wheeler, James / Robertson, Andrew / Dell'Acqua, Flavio / Smith, Marcus S / Williams, Steven C R

Scientific reports

2020 Volume 10, Issue 1, Page(s) 10116

Abstract: It is unclear to what extent cerebellar networks show long-term plasticity and accompanied changes in cortical structures. Using drumming as a demanding multimodal motor training, we compared cerebellar lobular volume and white matter microstructure, as ... ...

Abstract	It is unclear to what extent cerebellar networks show long-term plasticity and accompanied changes in cortical structures. Using drumming as a demanding multimodal motor training, we compared cerebellar lobular volume and white matter microstructure, as well as cortical thickness of 15 healthy non-musicians before and after learning to drum, and 16 age matched novice control participants. After 8 weeks of group drumming instruction, 3 ×30 minutes per week, we observed the cerebellum significantly changing its grey (volume increase of left VIIIa, relative decrease of VIIIb and vermis Crus I volume) and white matter microstructure in the inferior cerebellar peduncle. These plastic cerebellar changes were complemented by changes in cortical thickness (increase in left paracentral, right precuneus and right but not left superior frontal thickness), suggesting an interplay of cerebellar learning with cortical structures enabled through cerebellar pathways.
MeSH term(s)	Adolescent ; Brain/physiology ; Brain Mapping/methods ; Cerebellar Cortex/physiology ; Cerebellum/physiology ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Magnetic Resonance Imaging/methods ; Male ; Motor Activity/physiology ; Music Therapy/methods ; Neuronal Plasticity/physiology ; Parietal Lobe/physiology ; White Matter/physiology ; Young Adult
Language	English
Publishing date	2020-06-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-65877-2
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Article ; Online: Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins.

Van Nostrand, Eric L / Pratt, Gabriel A / Yee, Brian A / Wheeler, Emily C / Blue, Steven M / Mueller, Jasmine / Park, Samuel S / Garcia, Keri E / Gelboin-Burkhart, Chelsea / Nguyen, Thai B / Rabano, Ines / Stanton, Rebecca / Sundararaman, Balaji / Wang, Ruth / Fu, Xiang-Dong / Graveley, Brenton R / Yeo, Gene W

Genome biology

2020 Volume 21, Issue 1, Page(s) 90

Abstract: Background: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but ... ...

Abstract	Background: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. Results: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multicopy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites, and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation, enabling identification of branch points with single-nucleotide resolution, and provides genome-wide validation for a branch point-based scanning model for 3' splice site recognition. Finally, we show that eCLIP peak co-occurrences across RBPs enable the discovery of novel co-interacting RBPs. Conclusions: This work reveals novel insights into RNA biology by integrated analysis of eCLIP profiling of 150 RBPs with distinct functions. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.
MeSH term(s)	Binding Sites ; Hep G2 Cells ; Humans ; Immunoprecipitation ; Introns ; K562 Cells ; RNA/metabolism ; RNA Processing, Post-Transcriptional ; RNA Splicing ; RNA, Ribosomal/metabolism ; RNA-Binding Proteins/metabolism ; Repetitive Sequences, Nucleic Acid ; Retroelements ; Spliceosomes/metabolism
Chemical Substances	RNA, Ribosomal ; RNA-Binding Proteins ; Retroelements ; RNA (63231-63-0)
Language	English
Publishing date	2020-04-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-020-01982-9
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Article ; Online: Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination-United States, December 2020 to August 2021.

See, Isaac / Lale, Allison / Marquez, Paige / Streiff, Michael B / Wheeler, Allison P / Tepper, Naomi K / Woo, Emily Jane / Broder, Karen R / Edwards, Kathryn M / Gallego, Ruth / Geller, Andrew I / Jackson, Kelly A / Sharma, Shashi / Talaat, Kawsar R / Walter, Emmanuel B / Akpan, Imo J / Ortel, Thomas L / Urrutia, Victor C / Walker, Shannon C /

Yui, Jennifer C / Shimabukuro, Tom T / Mba-Jonas, Adamma / Su, John R / Shay, David K

Annals of internal medicine

2022 Volume 175, Issue 4, Page(s) 513–522

Abstract: Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of ... ...

Abstract	Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. Objective: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. Design: Case series. Setting: United States. Patients: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. Measurements: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. Results: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S ( Limitations: Underreporting and incomplete case follow-up. Conclusion: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. Primary funding source: Centers for Disease Control and Prevention.
MeSH term(s)	Ad26COVS1/adverse effects ; Adolescent ; Adult ; Aged ; COVID-19/epidemiology ; COVID-19 Vaccines/adverse effects ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; Syndrome ; Thrombocytopenia/chemically induced ; Thrombocytopenia/epidemiology ; Thrombosis/chemically induced ; Thrombosis/etiology ; United States/epidemiology ; Vaccination/adverse effects ; Vaccines/adverse effects ; Young Adult
Chemical Substances	Ad26COVS1 ; COVID-19 Vaccines ; RNA, Messenger ; Vaccines
Language	English
Publishing date	2022-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M21-4502
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Article ; Online: Drum training induces long-term plasticity in the cerebellum and connected cortical thickness

Muriel M. K. Bruchhage / Ali Amad / Stephen B. Draper / Jade Seidman / Luis Lacerda / Pedro Luque Laguna / Ruth G. Lowry / James Wheeler / Andrew Robertson / Flavio Dell’Acqua / Marcus S. Smith / Steven C. R. Williams

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 10

Abstract: Abstract It is unclear to what extent cerebellar networks show long-term plasticity and accompanied changes in cortical structures. Using drumming as a demanding multimodal motor training, we compared cerebellar lobular volume and white matter ... ...

Abstract	Abstract It is unclear to what extent cerebellar networks show long-term plasticity and accompanied changes in cortical structures. Using drumming as a demanding multimodal motor training, we compared cerebellar lobular volume and white matter microstructure, as well as cortical thickness of 15 healthy non-musicians before and after learning to drum, and 16 age matched novice control participants. After 8 weeks of group drumming instruction, 3 ×30 minutes per week, we observed the cerebellum significantly changing its grey (volume increase of left VIIIa, relative decrease of VIIIb and vermis Crus I volume) and white matter microstructure in the inferior cerebellar peduncle. These plastic cerebellar changes were complemented by changes in cortical thickness (increase in left paracentral, right precuneus and right but not left superior frontal thickness), suggesting an interplay of cerebellar learning with cortical structures enabled through cerebellar pathways.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
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Article ; Online: Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis.

Krach, Florian / Wheeler, Emily C / Regensburger, Martin / Boerstler, Tom / Wend, Holger / Vu, Anthony Q / Wang, Ruth / Reischl, Stephanie / Boldt, Karsten / Batra, Ranjan / Aigner, Stefan / Ravits, John / Winkler, Juergen / Yeo, Gene W / Winner, Beate

Acta neuropathologica

2022 Volume 144, Issue 3, Page(s) 413–435

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by aberrant alternative splicing (AS). Nuclear loss and cytoplasmic accumulation of the splicing factor TDP-43 in motor neurons (MN) are hallmarks of ALS at late stages of the disease. ... ...

Abstract	Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by aberrant alternative splicing (AS). Nuclear loss and cytoplasmic accumulation of the splicing factor TDP-43 in motor neurons (MN) are hallmarks of ALS at late stages of the disease. However, it is unknown if altered AS is present before TDP-43 pathology occurs. Here, we investigate altered AS and its origins in early stages of ALS using human induced pluripotent stem cell-derived motor neurons (MNs) from sporadic and familial ALS patients. We find high levels of the RNA-binding proteins NOVA1, NOVA2, and RBFOX2 in the insoluble protein fractions and observe that AS events in ALS-associated MNs are enriched for binding sites of these proteins. Our study points to an early disrupted function of NOVA1 that drives AS changes in a complex fashion, including events caused by a consistent loss of NOVA1 function. NOVA1 exhibits increased cytoplasmic protein levels in early stage MNs without TDP-43 pathology in ALS postmortem tissue. As nuclear TDP-43 protein level depletes, NOVA1 is reduced. Potential indications for a reduction of NOVA1 also came from mice over-expressing TDP-43 lacking its nuclear localization signal and iPSC-MN stressed with puromycin. This study highlights that additional RBP-RNA perturbations in ALS occur in parallel to TDP-43.
MeSH term(s)	Alternative Splicing/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Animals ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuro-Oncological Ventral Antigen/genetics ; Neuro-Oncological Ventral Antigen/metabolism ; Nuclear Proteins/genetics ; RNA Splicing Factors/genetics ; RNA Splicing Factors/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Repressor Proteins/genetics
Chemical Substances	DNA-Binding Proteins ; NOVA1 protein, human ; NOVA2 protein, human ; Nerve Tissue Proteins ; Neuro-Oncological Ventral Antigen ; Nova1 protein, mouse ; Nuclear Proteins ; RBFOX2 protein, human ; RNA Splicing Factors ; RNA-Binding Proteins ; Rbfox2 protein, mouse ; Repressor Proteins ; TARDBP protein, human ; TDP-43 protein, mouse
Language	English
Publishing date	2022-07-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-022-02450-3
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Article ; Online: Motor Learning Induces Plasticity in the Resting Brain-Drumming Up a Connection.

Amad, Ali / Seidman, Jade / Draper, Stephen B / Bruchhage, Muriel M K / Lowry, Ruth G / Wheeler, James / Robertson, Andrew / Williams, Steven C R / Smith, Marcus S

Cerebral cortex (New York, N.Y. : 1991)

2017 Volume 27, Issue 3, Page(s) 2010–2021

Abstract: Neuroimaging methods have recently been used to investigate plasticity-induced changes in brain structure. However, little is known about the dynamic interactions between different brain regions after extensive coordinated motor learning such as drumming. ...

Abstract	Neuroimaging methods have recently been used to investigate plasticity-induced changes in brain structure. However, little is known about the dynamic interactions between different brain regions after extensive coordinated motor learning such as drumming. In this article, we have compared the resting-state functional connectivity (rs-FC) in 15 novice healthy participants before and after a course of drumming (30-min drumming sessions, 3 days a week for 8 weeks) and 16 age-matched novice comparison participants. To identify brain regions showing significant FC differences before and after drumming, without a priori regions of interest, a multivariate pattern analysis was performed. Drum training was associated with an increased FC between the posterior part of bilateral superior temporal gyri (pSTG) and the rest of the brain (i.e., all other voxels). These regions were then used to perform seed-to-voxel analysis. The pSTG presented an increased FC with the premotor and motor regions, the right parietal lobe and a decreased FC with the cerebellum. Perspectives and the potential for rehabilitation treatments with exercise-based intervention to overcome impairments due to brain diseases are also discussed.
MeSH term(s)	Adolescent ; Brain/diagnostic imaging ; Brain/physiology ; Brain Mapping ; Female ; Functional Laterality ; Humans ; Learning/physiology ; Magnetic Resonance Imaging ; Male ; Motor Skills/physiology ; Multivariate Analysis ; Music ; Neural Pathways/diagnostic imaging ; Neural Pathways/physiology ; Neuronal Plasticity/physiology ; Periodicity ; Rest ; Self Report ; Signal Processing, Computer-Assisted ; Young Adult
Language	English
Publishing date	2017-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhw048
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Article ; Online: Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

Eric L. Van Nostrand / Gabriel A. Pratt / Brian A. Yee / Emily C. Wheeler / Steven M. Blue / Jasmine Mueller / Samuel S. Park / Keri E. Garcia / Chelsea Gelboin-Burkhart / Thai B. Nguyen / Ines Rabano / Rebecca Stanton / Balaji Sundararaman / Ruth Wang / Xiang-Dong Fu / Brenton R. Graveley / Gene W. Yeo

Genome Biology, Vol 21, Iss 1, Pp 1-

2020 Volume 26

Abstract: Abstract Background A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but ... ...

Abstract	Abstract Background A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. Results Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multicopy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites, and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation, enabling identification of branch points with single-nucleotide resolution, and provides genome-wide validation for a branch point-based scanning model for 3′ splice site recognition. Finally, we show that eCLIP peak co-occurrences across RBPs enable the discovery of novel co-interacting RBPs. Conclusions This work reveals novel insights into RNA biology by integrated analysis of eCLIP profiling of 150 RBPs with distinct functions. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.
Keywords	eCLIP ; CLIP-seq ; RNA binding protein ; RNA processing ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
Subject code	004
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Case Series of Thrombosis with Thrombocytopenia Syndrome following COVID-19 vaccination--United States, December 2020-August 2021

medRxiv

Abstract: Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. TTS presents similarly to autoimmune heparin-induced thrombocytopenia. Twelve cases of ... ...

Abstract	Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. TTS presents similarly to autoimmune heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis following Janssen/Johnson & Johnson (Ad26.COV2.S) COVID-19 vaccination have been described. Objective: Describe surveillance data and reporting rates of TTS cases following COVID-19 vaccination. Design: Case series. Setting: United States Patients: Case-patients reported to the Vaccine Adverse Event Reporting System (VAERS) receiving COVID-19 vaccine from December 14, 2020 through August 31, 2021, with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction). If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for anti-platelet factor 4 antibody was required. Measurements: Reporting rates (cases/million vaccine doses) and descriptive epidemiology. Results: 52 TTS cases were confirmed following Ad26.COV2.S (n=50) or mRNA-based COVID-19 (n=2) vaccination. TTS reporting rates were 3.55per million (Ad26.COV2.S) and 0.0057 per million (mRNA-based COVID-19 vaccines). Median age of patients with TTS following Ad26.COV2.S vaccination was 43.5 years (range: 18-70); 70% were female. Both TTS cases following mRNA-based COVID-19 vaccination occurred in males aged >50 years. All cases following Ad26.COV2.S vaccination involved hospitalization including 32 (64%) admitted to an intensive care unit. Outcomes following Ad26.COV2.S vaccination included death (12%), discharge to post-acute care (16%), and discharge home (72%). Limitations: Under-reporting and incomplete case follow-up. Conclusion: TTS is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The lower reporting rate and different demographic characteristics for the two cases following mRNA-based COVID-19 vaccines suggest a potentially different pathogenesis or background occurrence.
Keywords	covid19
Language	English
Publishing date	2021-11-14
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.11.10.21266063
Database	COVID19

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Article: Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

Genome biology. 2020 Dec., v. 21, no. 1

2020

Abstract: BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but ... ...

Abstract	BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. RESULTS: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multicopy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites, and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation, enabling identification of branch points with single-nucleotide resolution, and provides genome-wide validation for a branch point-based scanning model for 3′ splice site recognition. Finally, we show that eCLIP peak co-occurrences across RBPs enable the discovery of novel co-interacting RBPs. CONCLUSIONS: This work reveals novel insights into RNA biology by integrated analysis of eCLIP profiling of 150 RBPs with distinct functions. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.
Keywords	RNA-binding proteins ; crosslinking ; mechanism of action ; messenger RNA ; models ; precipitin tests ; ribosomal RNA ; spliceosomes
Language	English
Dates of publication	2020-12
Size	p. 90.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6906
ISSN (online)	1474-760X
ISSN	1465-6906
DOI	10.1186/s13059-020-01982-9
Database	NAL-Catalogue (AGRICOLA)

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