Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms. / Wedge, Eileen; Ahmadov, Ulvi; Hansen, Thomas B.; Gao, Zongliang; Tulstrup, Morten; Côme, Christophe; Nonavinkere Srivatsan, Sridhar; Ahmed, Tanzir; Jespersen, Jakob S.; Schlotmann, Balthasar C.; Schöllkopf, Claudia; Raaschou-Jensen, Klas; Ødum, Niels; Kjems, Jørgen; Bak, Rasmus O.; Walter, Matthew J.; Grønbæk, Kirsten; Kristensen, Lasse S.

In: Leukemia, Vol. 37, 2023, p. 1113-1125.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Wedge, E, Ahmadov, U, Hansen, TB, Gao, Z, Tulstrup, M, Côme, C, Nonavinkere Srivatsan, S, Ahmed, T, Jespersen, JS, Schlotmann, BC, Schöllkopf, C, Raaschou-Jensen, K, Ødum, N, Kjems, J, Bak, RO, Walter, MJ, Grønbæk, K & Kristensen, LS 2023, 'Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms', Leukemia, vol. 37, pp. 1113-1125. https://doi.org/10.1038/s41375-023-01866-4

APA

Wedge, E., Ahmadov, U., Hansen, T. B., Gao, Z., Tulstrup, M., Côme, C., Nonavinkere Srivatsan, S., Ahmed, T., Jespersen, J. S., Schlotmann, B. C., Schöllkopf, C., Raaschou-Jensen, K., Ødum, N., Kjems, J., Bak, R. O., Walter, M. J., Grønbæk, K., & Kristensen, L. S. (2023). Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms. Leukemia, 37, 1113-1125. https://doi.org/10.1038/s41375-023-01866-4

Vancouver

Wedge E, Ahmadov U, Hansen TB, Gao Z, Tulstrup M, Côme C et al. Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms. Leukemia. 2023;37:1113-1125. https://doi.org/10.1038/s41375-023-01866-4

Author

Wedge, Eileen ; Ahmadov, Ulvi ; Hansen, Thomas B. ; Gao, Zongliang ; Tulstrup, Morten ; Côme, Christophe ; Nonavinkere Srivatsan, Sridhar ; Ahmed, Tanzir ; Jespersen, Jakob S. ; Schlotmann, Balthasar C. ; Schöllkopf, Claudia ; Raaschou-Jensen, Klas ; Ødum, Niels ; Kjems, Jørgen ; Bak, Rasmus O. ; Walter, Matthew J. ; Grønbæk, Kirsten ; Kristensen, Lasse S. / Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms. In: Leukemia. 2023 ; Vol. 37. pp. 1113-1125.

Bibtex

@article{c0cbb222975341f9879ca3d8f763e8bd,
title = "Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms",
abstract = "Mutations in U2AF1 are relatively common in myelodysplastic neoplasms (MDS) and are associated with an inferior prognosis, but the molecular mechanisms underlying this are not fully elucidated. Circular RNAs (circRNAs) have been implicated in cancer, but it is unknown how mutations in splicing factors may impact on circRNA biogenesis. Here, we used RNA-sequencing to investigate the effects of U2AF1 mutations on circRNA expression in K562 cells with a doxycycline-inducible U2AF1S34 mutation, in a mouse model with a doxycycline-inducible U2AF1S34 mutation, and in FACS-sorted CD34+ bone marrow cells from MDS patients with either U2AF1S34 or U2AF1Q157 mutations. In all contexts, we found an increase in global circRNA levels in the U2AF1-mutated setting, which was independent of expression changes in the cognate linear host genes. In patients, the U2AF1S34 and U2AF1Q157 mutations were both associated with an overall increased expression of circRNAs. circRNAs generated by a non-Alu-mediated mechanism generally showed the largest increase in expression levels. Several well-described cancer-associated circRNAs, including circZNF609 and circCSNK1G3, were upregulated in MDS patients with U2AF1 mutations compared to U2AF1-wildtype MDS controls. In conclusion, high circRNA expression is observed in association with U2AF1 mutations in three biological systems, presenting an interesting possibility for biomarker and therapeutic investigation.",
author = "Eileen Wedge and Ulvi Ahmadov and Hansen, {Thomas B.} and Zongliang Gao and Morten Tulstrup and Christophe C{\^o}me and {Nonavinkere Srivatsan}, Sridhar and Tanzir Ahmed and Jespersen, {Jakob S.} and Schlotmann, {Balthasar C.} and Claudia Sch{\"o}llkopf and Klas Raaschou-Jensen and Niels {\O}dum and J{\o}rgen Kjems and Bak, {Rasmus O.} and Walter, {Matthew J.} and Kirsten Gr{\o}nb{\ae}k and Kristensen, {Lasse S.}",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2023",
doi = "10.1038/s41375-023-01866-4",
language = "English",
volume = "37",
pages = "1113--1125",
journal = "Leukemia",
issn = "0887-6924",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Impact of U2AF1 mutations on circular RNA expression in myelodysplastic neoplasms

AU - Wedge, Eileen

AU - Ahmadov, Ulvi

AU - Hansen, Thomas B.

AU - Gao, Zongliang

AU - Tulstrup, Morten

AU - Côme, Christophe

AU - Nonavinkere Srivatsan, Sridhar

AU - Ahmed, Tanzir

AU - Jespersen, Jakob S.

AU - Schlotmann, Balthasar C.

AU - Schöllkopf, Claudia

AU - Raaschou-Jensen, Klas

AU - Ødum, Niels

AU - Kjems, Jørgen

AU - Bak, Rasmus O.

AU - Walter, Matthew J.

AU - Grønbæk, Kirsten

AU - Kristensen, Lasse S.

N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2023

Y1 - 2023

N2 - Mutations in U2AF1 are relatively common in myelodysplastic neoplasms (MDS) and are associated with an inferior prognosis, but the molecular mechanisms underlying this are not fully elucidated. Circular RNAs (circRNAs) have been implicated in cancer, but it is unknown how mutations in splicing factors may impact on circRNA biogenesis. Here, we used RNA-sequencing to investigate the effects of U2AF1 mutations on circRNA expression in K562 cells with a doxycycline-inducible U2AF1S34 mutation, in a mouse model with a doxycycline-inducible U2AF1S34 mutation, and in FACS-sorted CD34+ bone marrow cells from MDS patients with either U2AF1S34 or U2AF1Q157 mutations. In all contexts, we found an increase in global circRNA levels in the U2AF1-mutated setting, which was independent of expression changes in the cognate linear host genes. In patients, the U2AF1S34 and U2AF1Q157 mutations were both associated with an overall increased expression of circRNAs. circRNAs generated by a non-Alu-mediated mechanism generally showed the largest increase in expression levels. Several well-described cancer-associated circRNAs, including circZNF609 and circCSNK1G3, were upregulated in MDS patients with U2AF1 mutations compared to U2AF1-wildtype MDS controls. In conclusion, high circRNA expression is observed in association with U2AF1 mutations in three biological systems, presenting an interesting possibility for biomarker and therapeutic investigation.

AB - Mutations in U2AF1 are relatively common in myelodysplastic neoplasms (MDS) and are associated with an inferior prognosis, but the molecular mechanisms underlying this are not fully elucidated. Circular RNAs (circRNAs) have been implicated in cancer, but it is unknown how mutations in splicing factors may impact on circRNA biogenesis. Here, we used RNA-sequencing to investigate the effects of U2AF1 mutations on circRNA expression in K562 cells with a doxycycline-inducible U2AF1S34 mutation, in a mouse model with a doxycycline-inducible U2AF1S34 mutation, and in FACS-sorted CD34+ bone marrow cells from MDS patients with either U2AF1S34 or U2AF1Q157 mutations. In all contexts, we found an increase in global circRNA levels in the U2AF1-mutated setting, which was independent of expression changes in the cognate linear host genes. In patients, the U2AF1S34 and U2AF1Q157 mutations were both associated with an overall increased expression of circRNAs. circRNAs generated by a non-Alu-mediated mechanism generally showed the largest increase in expression levels. Several well-described cancer-associated circRNAs, including circZNF609 and circCSNK1G3, were upregulated in MDS patients with U2AF1 mutations compared to U2AF1-wildtype MDS controls. In conclusion, high circRNA expression is observed in association with U2AF1 mutations in three biological systems, presenting an interesting possibility for biomarker and therapeutic investigation.

U2 - 10.1038/s41375-023-01866-4

DO - 10.1038/s41375-023-01866-4

M3 - Journal article

C2 - 36922625

AN - SCOPUS:85149954219

VL - 37

SP - 1113

EP - 1125

JO - Leukemia

JF - Leukemia

SN - 0887-6924

ER -

ID: 339993493