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

Nucleic Acids Research
Mikalai Lapkouski, B Martin Hällberg

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, mtPAP's dimerization requirement remains enigmatic. Here, we show the structural basis for mtPAP's 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.

References

Aug 1, 1995·Computer Applications in the Biosciences : CABIOS·M G Claros
Aug 22, 2003·Protein Science : a Publication of the Protein Society·Katherine A Kantardjieff, Bernhard Rupp
Nov 18, 2004·Nucleic Acids Research·Rafal TomeckiPiotr P Stepien
Jul 19, 2005·Molecular and Cellular Biology·Shimyn SlomovicGadi Schuster
Aug 25, 2006·Acta Crystallographica. Section D, Biological Crystallography·Kevin Cowtan
Dec 27, 2006·Journal of Molecular Biology·Jason StagnoRuslan Aphasizhev
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Sep 18, 2007·RNA·Georges Martin, Walter Keller
Mar 4, 2008·Biochimica Et Biophysica Acta·Takashi NagaikeTakuya Ueda
May 12, 2009·Nature Structural & Molecular Biology·Olivia S Rissland, Chris J Norbury
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Alexei Vagin, Alexei Teplyakov
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 10, 2010·Biochimica Et Biophysica Acta·Richard J TemperleyZofia M Chrzanowska-Lightowlers
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·Kevin Cowtan
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Oct 26, 2010·American Journal of Human Genetics·Andrew H CrosbyRobert N Lightowlers
Apr 2, 2011·The Journal of Biological Chemistry·Linda J Wheeler, Christopher K Mathews
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Aug 23, 2011·Cell·Tim R MercerJohn S Mattick
May 23, 2012·Structure·Paola Munoz-TelloStéphane Thore
May 26, 2012·Science·P Andrew Karplus, Kay Diederichs
Jul 4, 2012·Nature Structural & Molecular Biology·Luke A YatesRobert J C Gilbert
Aug 14, 2012·Nucleic Acids Research·Bradley M LundeAnton Meinhart
Mar 19, 2013·The EMBO Journal·Michal MaleckiCecília M Arraiano
Nov 23, 2013·International Journal of Molecular Sciences·Maria Grazia RomanelliPatricia Marie-Jeanne Lievens
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Jul 30, 2014·Nucleic Acids Research·Sébastien SagnolPascal de Santa Barbara
Aug 5, 2014·Cell Metabolism·B Martin Hällberg, Nils-Göran Larsson
Dec 7, 2014·Cell·Jaechul LimV Narry Kim

❮ Previous
Next ❯

Citations

Apr 12, 2017·Scientific Reports·Karin WalldénB Martin Hällberg
Jun 8, 2017·Nature Communications·Seisuke YamashitaKozo Tomita
Jul 4, 2017·Nature Structural & Molecular Biology·Christopher R FaehnleLeemor Joshua-Tor
Oct 13, 2018·EMBO Reports·Norihiko FuruyaNobutaka Hattori
Nov 30, 2018·Frontiers in Genetics·Yuka Yashiro, Kozo Tomita
Jul 22, 2018·Essays in Biochemistry·Aaron R D'Souza, Michal Minczuk
Nov 5, 2020·Wiley Interdisciplinary Reviews. RNA·Vladyslava Liudkovska, Andrzej Dziembowski
Dec 17, 2020·Biomedicines·Olga BuneevaAlexei Medvedev
Aug 8, 2021·International Journal of Molecular Sciences·Joseph E FriedlanderHui Feng
Aug 17, 2021·Frontiers in Genetics·Xinran CuiYadong Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
PISA

Software Mentioned

XDS
PyMOL
COOT
MOLREP
MOLPROBITY
BUCCANEER
REFMAC
ProtSkin
POINTLESS
PARROT

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.