@misc{10481/95408,
year = {2023},
month = {7},
url = {https://hdl.handle.net/10481/95408},
abstract = {Retrotransposons have generated about half of the human genome and LINE-1s (L1s) are
the only autonomously active retrotransposons. The cell has evolved an arsenal of defense
mechanisms to protect against retrotransposition with factors we are only beginning to
understand. In this study, we investigate Zinc Finger CCHC-Type Containing 3 (ZCCHC3),
a gag-like zinc knuckle protein recently reported to function in the innate immune response
to infecting viruses. We show that ZCCHC3 also severely restricts human retrotransposons
and associates with the L1 ORF1p ribonucleoprotein particle. We identify ZCCHC3 as a
bona fide stress granule protein, and its association with LINE-1 is further supported by colocalization
with L1 ORF1 protein in stress granules, dense cytoplasmic aggregations of proteins
and RNAs that contain stalled translation pre-initiation complexes and form when the
cell is under stress. Our work also draws links between ZCCHC3 and the anti-viral and retrotransposon
restriction factors Mov10 RISC Complex RNA Helicase (MOV10) and Zinc Finger
CCCH-Type, Antiviral 1 (ZC3HAV1, also called ZAP). Furthermore, collective evidence
from subcellular localization, co-immunoprecipitation, and velocity gradient centrifugation
connects ZCCHC3 with the RNA exosome, a multi-subunit ribonuclease complex capable
of degrading various species of RNA molecules and that has previously been linked with retrotransposon
control.},
organization = {Grant from the
U.S. National Institutes of Health National Institute
of Aging (R21AG056840)},
organization = {Grant from Eunice Kennedy
Shriver National Institute of Child Health and
Human Development (R21HD083915)},
organization = {NIH NIGMS grant
R01GM099875},
organization = {European Research Council (ERC-Consolidator ERC-STG-2012-309433), the
Government of Spain (MINECO-FEDER SAF2017-89745-R and PID2021-128934NB-I00)},
organization = {Andalusian Regional Government (PAIDI P12-CTS-2256 and P18-RT-5067)},
publisher = {Plos One},
title = {ZCCHC3 is a stress granule zinc knuckle protein that strongly suppresses LINE-1 retrotransposition},
doi = {10.1371/journal.pgen.1010795},
author = {Goodier, John L. and Wan, Han and Soares, Alisha O. and Sánchez, Laura and Selser, John Michael and Pereira, Gavin C. and Karma, Sadik and García Pérez, José Luis and Kazazian Jr, Haig H. and García Cañadas, Marta},
}