Structure of mitochondrial poly(A) RNA polymerase reveals the structural basis for dimerization, ATP selectivity and the SPAX4 disease phenotype.

Lapkouski, Mikalai; Haellberg, Martin

doi:10.1093/nar/gkv861

Journal Article

PUBDB-2015-04674

Structure of mitochondrial poly(A) RNA polymerase reveals the structural basis for dimerization, ATP selectivity and the SPAX4 disease phenotype.

Lapkouski, M.EMBL*DESY* ; Haellberg, M. (Corresponding author)>Extern*EMBL*

2015
Oxford Univ. Press8619 Oxford

Nucleic acids symposium series 43(18), 9065 - 9075 (2015) [10.1093/nar/gkv861]

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Please use a persistent id in citations: doi:10.1093/nar/gkv861

Abstract: Polyadenylation, performed by poly(A) polymerases (PAPs), is a ubiquitous post-transcriptional modification that plays key roles in multiple aspects of RNA metabolism. Although cytoplasmic and nuclear PAPs have been studied extensively, the mechanism by which mitochondrial PAP (mtPAP) selects adenosine triphosphate over other nucleotides is unknown. Furthermore, mtPAP is unique because it acts as a dimer. However, mtPAPs dimerization requirement remains enigmatic. Here, we show the structural basis for mtPAPs nucleotide selectivity, dimerization and catalysis. Our structures reveal an intricate dimerization interface that features an RNA-recognition module formed through strand complementation. Further, we propose the structural basis for the N478D mutation that drastically reduces the length of poly(A) tails on mitochondrial mRNAs in patients with spastic ataxia 4 (SPAX4), a severe and progressive neurodegenerative disease.

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