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Bhattarai, Devi Prasad
Publikationer (4 of 4) Visa alla publikationer
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
Öppna denna publikation i ny flik eller fönster >>METTL3 regulates breast cancer-associated alternative splicing switches
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2023 (Engelska)Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 42, s. 911-925Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2023
Nationell ämneskategori
Biokemi och molekylärbiologi Bioinformatik och systembiologi Cancer och onkologi
Forskningsämne
molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-194175 (URN)10.1038/s41388-023-02602-z (DOI)000925962300003 ()36725888 (PubMedID)2-s2.0-85147175928 (Scopus ID)
Forskningsfinansiär
Knut och Alice Wallenbergs StiftelseRegion VästerbottenVetenskapsrådet, 2017-01636Cancerfonden, 19 0337 PjKempestiftelserna, SMK-1766Cancerforskningsfonden i Norrland, LP 16-2126
Tillgänglig från: 2022-04-26 Skapad: 2022-04-26 Senast uppdaterad: 2024-04-08Bibliografiskt granskad
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
Öppna denna publikation i ny flik eller fönster >>m6A RNA immunoprecipitation followed by high-throughput sequencing to map N6-Methyladenosine
2022 (Engelska)Ingår i: Post-transcriptional gene regulation / [ed] Erik Dassi, Humana Press, 2022, 3, , s. 8s. 355-362Kapitel i bok, del av antologi (Refereegranskat)
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.

Ort, förlag, år, upplaga, sidor
Humana Press, 2022. s. 8 Upplaga: 3
Serie
Methods in Molecular Biology (MIMB), ISSN 1064-3745, E-ISSN 1940-6029 ; 2404
Nyckelord
Epitranscriptomics, MeRIP-seq or m6A-seq, METTL3, N6-Methyladenosine
Nationell ämneskategori
Cell- och molekylärbiologi Biokemi och molekylärbiologi
Identifikatorer
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)
Forskningsfinansiär
Region VästerbottenKnut och Alice Wallenbergs StiftelseVetenskapsrådet, 2017-01636Kempestiftelserna, 19 0337 Pj, SMK-1766
Tillgänglig från: 2021-11-16 Skapad: 2021-11-16 Senast uppdaterad: 2022-03-08Bibliografiskt granskad
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.
Öppna denna publikation i ny flik eller fönster >>ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export
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2022 (Engelska)Ingår i: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 23, nr 3, artikel-id e53191Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2022
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-191672 (URN)10.15252/embr.202153191 (DOI)000743102200001 ()35037361 (PubMedID)2-s2.0-85122763926 (Scopus ID)
Tillgänglig från: 2022-01-21 Skapad: 2022-01-21 Senast uppdaterad: 2024-04-08Bibliografiskt granskad
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.
Öppna denna publikation i ny flik eller fönster >>Reshaping the role of METTL3 in breast tumorigenesis
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Cellbiologi Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-201048 (URN)
Tillgänglig från: 2022-11-16 Skapad: 2022-11-16 Senast uppdaterad: 2024-03-22
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