TY  - JOUR
AU  - Lapkouski, Mikalai
AU  - Haellberg, Martin
TI  - Structure of mitochondrial poly(A) RNA polymerase reveals the structural basis for dimerization, ATP selectivity and the SPAX4 disease phenotype.
JO  - Nucleic acids symposium series
VL  - 43
IS  - 18
SN  - 1362-4962
CY  - Oxford
PB  - Oxford Univ. Press8619
M1  - PUBDB-2015-04674
SP  - 9065 - 9075
PY  - 2015
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:26319014
C2  - pmc:PMC4605311
UR  - <Go to ISI:>//WOS:000366406500043
DO  - DOI:10.1093/nar/gkv861
UR  - https://bib-pubdb1.desy.de/record/276466
ER  -