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Bhattarai, Devi Prasad
Publications (4 of 4) Show all publications
Achour, C., Bhattarai, D. P., Groza, P., Roman, Á.-C. & Aguilo, F. (2023). METTL3 regulates breast cancer-associated alternative splicing switches. Oncogene, 42, 911-925
Open this publication in new window or tab >>METTL3 regulates breast cancer-associated alternative splicing switches
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2023 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 42, p. 911-925Article in journal (Refereed) Published
Abstract [en]

Alternative splicing (AS) enables differential inclusion of exons from a given transcript, thereby contributing to the transcriptome and proteome diversity. Aberrant AS patterns play major roles in the development of different pathologies, including breast cancer. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, influences tumor progression and metastasis of breast cancer, and it has been recently linked to AS regulation. Here, we identify a specific AS signature associated with breast tumorigenesis in vitro. We characterize for the first time the role of METTL3 in modulating breast cancer-associated AS programs, expanding the role of the m6A-methyltransferase in tumorigenesis. Specifically, we find that both m6A deposition in splice site boundaries and in splicing and transcription factor transcripts, such as MYC, direct AS switches of specific breast cancer-associated transcripts. Finally, we show that five of the AS events validated in vitro are associated with a poor overall survival rate for patients with breast cancer, suggesting the use of these AS events as a novel potential prognostic biomarker.

Place, publisher, year, edition, pages
Nature Publishing Group, 2023
National Category
Biochemistry and Molecular Biology Bioinformatics and Systems Biology Cancer and Oncology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-194175 (URN)10.1038/s41388-023-02602-z (DOI)000925962300003 ()36725888 (PubMedID)2-s2.0-85147175928 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationRegion VästerbottenSwedish Research Council, 2017-01636Swedish Cancer Society, 19 0337 PjThe Kempe Foundations, SMK-1766Cancerforskningsfonden i Norrland, LP 16-2126
Available from: 2022-04-26 Created: 2022-04-26 Last updated: 2024-04-08Bibliographically approved
Bhattarai, D. P. & Aguilo, F. (2022). m6A RNA immunoprecipitation followed by high-throughput sequencing to map N6-Methyladenosine (3ed.). In: Erik Dassi (Ed.), Post-transcriptional gene regulation: (pp. 355-362). Humana Press
Open this publication in new window or tab >>m6A RNA immunoprecipitation followed by high-throughput sequencing to map N6-Methyladenosine
2022 (English)In: Post-transcriptional gene regulation / [ed] Erik Dassi, Humana Press, 2022, 3, , p. 8p. 355-362Chapter in book (Refereed)
Abstract [en]

N6-methyladenosine (m6A) is the most abundant internal modification on messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in eukaryotes. It influences gene expression by regulating RNA processing, nuclear export, mRNA decay, and translation. Hence, m6A controls fundamental cellular processes, and dysregulated deposition of m6A has been acknowledged to play a role in a broad range of human diseases, including cancer. m6A RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq or m6A-seq) is a powerful technique to map m6A in a transcriptome-wide level. After immunoprecipitation of fragmented polyadenylated (poly(A)+) rich RNA by using specific anti-m6A antibodies, both the immunoprecipitated RNA fragments together with the input control are subjected to massively parallel sequencing. The generation of such comprehensive methylation profiles of signal enrichment relative to input control is necessary in order to better comprehend the pathogenesis behind aberrant m6A deposition.

Place, publisher, year, edition, pages
Humana Press, 2022. p. 8 Edition: 3
Series
Methods in Molecular Biology (MIMB), ISSN 1064-3745, E-ISSN 1940-6029 ; 2404
Keywords
Epitranscriptomics, MeRIP-seq or m6A-seq, METTL3, N6-Methyladenosine
National Category
Cell and Molecular Biology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-189549 (URN)10.1007/978-1-0716-1851-6_19 (DOI)2-s2.0-85118431040 (Scopus ID)9781071618516 (ISBN)9781071618509 (ISBN)
Funder
Region VästerbottenKnut and Alice Wallenberg FoundationSwedish Research Council, 2017-01636The Kempe Foundations, 19 0337 Pj, SMK-1766
Available from: 2021-11-16 Created: 2021-11-16 Last updated: 2022-03-08Bibliographically approved
Malla, S., Bhattarai, D. P., Groza, P., Melguizo-Sanchis, D., Atanasoai, I., Martinez Gamero, C., . . . Aguilo, F. (2022). ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export. EMBO Reports, 23(3), Article ID e53191.
Open this publication in new window or tab >>ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export
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2022 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 23, no 3, article id e53191Article in journal (Refereed) Published
Abstract [en]

The pluripotent state is not solely governed by the action of the core transcription factors OCT4, SOX2, and NANOG, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize its role in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, mouse ZFP207 does not transcriptionally regulate neuronal and stem cell-related genes but exerts its effects by controlling AS networks and by acting as an RBP. Our study expands the role of ZFP207 in maintaining ESC identity, and underscores the functional versatility of ZFP207 in regulating neural fate commitment.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-191672 (URN)10.15252/embr.202153191 (DOI)000743102200001 ()35037361 (PubMedID)2-s2.0-85122763926 (Scopus ID)
Available from: 2022-01-21 Created: 2022-01-21 Last updated: 2024-04-08Bibliographically approved
Achour, C., Bhattarai, D. P., Esteva-Socias, M., Rodriguez-Barrueco, R., Malla, S., Seier, K., . . . Aguilo, F.Reshaping the role of METTL3 in breast tumorigenesis.
Open this publication in new window or tab >>Reshaping the role of METTL3 in breast tumorigenesis
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(English)Manuscript (preprint) (Other academic)
National Category
Cell Biology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-201048 (URN)
Available from: 2022-11-16 Created: 2022-11-16 Last updated: 2024-03-22
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