CDIN1-Codanin-1 complex defective in congenital dyserythropoietic anaemia type I is an RNA nuclease

Congenital Dyserythropoietic Anaemia type I (CDA-I) is a rare inherited disorder of erythropoiesis, in which erythroid cells display a unique nuclear phenotype referred to as 'spongy' heterochromatin. The molecular basis of CDA-I remains unknown, with most cases of CDA-I caused by mutations in CDAN1, encoding Codanin-1, or CDIN1, encoding for Codanin-1-interacting nuclease 1 (CDIN1). To date, very little is known about the function of CDA-I disease proteins and the mechanism by which their associated mutations cause disease. Here, we demonstrate that endogenous CDIN1 interacts with Codanin-1, to form a stable complex. Structural and functional analysis of this complex reveals that the CDIN1-Codanin-1 complex is an RNA nuclease. We shed light on the key mechanistic features of the complex using biochemical and biophysical approaches, complemented by all-atom molecular dynamics (MD) structural simulations. We identify various functional consequences of founder patient mutations on the RNA nuclease activity of CDIN1, providing a framework for understanding the pathophysiology and developing therapeutic strategies for CDA-I.

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Journal
Nature Communications
Published
2026-07-02
DOI
https://doi.org/10.1038/s41467-026-74766-7
Primary Topic
Erythrocyte Function and Pathophysiology
Type
article
Field-Weighted Citation Impact
0.00

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article

CDIN1-Codanin-1 complex defective in congenital dyserythropoietic anaemia type I is an RNA nuclease

H. Aitkenhead, Douglas R. Higgs, Veronica J. Buckle, Peter J. McHugh et al.
Nature Communications
Erythrocyte Function and Pathophysiology
article

CDIN1-Codanin-1 complex defective in congenital dyserythropoietic anaemia type I is an RNA nuclease

H. Aitkenhead, Douglas R. Higgs, Veronica J. Buckle, Peter J. McHugh, Aude-Anaïs Olijnik, Gemma Moir-Meyer, Sanja Brolih, Caroline Scott, O. Gileadi, J.A. Newman, Y. Yosaatmadja, A.E. Gavard, Christian Babbs, Fernanda Duarte, Hafiz Saqib Ali, Noemi Roy
article en

Abstract

Congenital Dyserythropoietic Anaemia type I (CDA-I) is a rare inherited disorder of erythropoiesis, in which erythroid cells display a unique nuclear phenotype referred to as 'spongy' heterochromatin. The molecular basis of CDA-I remains unknown, with most cases of CDA-I caused by mutations in CDAN1, encoding Codanin-1, or CDIN1, encoding for Codanin-1-interacting nuclease 1 (CDIN1). To date, very little is known about the function of CDA-I disease proteins and the mechanism by which their associated mutations cause disease. Here, we demonstrate that endogenous CDIN1 interacts with Codanin-1, to form a stable complex. Structural and functional analysis of this complex reveals that the CDIN1-Codanin-1 complex is an RNA nuclease. We shed light on the key mechanistic features of the complex using biochemical and biophysical approaches, complemented by all-atom molecular dynamics (MD) structural simulations. We identify various functional consequences of founder patient mutations on the RNA nuclease activity of CDIN1, providing a framework for understanding the pathophysiology and developing therapeutic strategies for CDA-I.

Nature Communications
Karolinska University Hospital (SE), University of Auckland (NZ), Churchill Hospital (GB), Diamond Light Source (GB), John Radcliffe Hospital (GB), University of Oxford (GB), MRC Weatherall Institute of Molecular Medicine (GB), MRC Human Immunology Unit (GB)
Action Medical Research, Cancer Research UK, National Institute for Health and Care Research, University of Oxford, Medical Research Council
Openalex Percentile: Top 8%
Erythrocyte Function and Pathophysiology
DOIOpen Access PDFOpenAlex
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