---
_id: '14644'
abstract:
- lang: eng
text: Transcription by RNA polymerase II (Pol II) can be repressed by noncoding
RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs
repress transcription remains unclear. Here we present cryo-electron microscopy
structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA
and RNA bind to Pol II during transcription elongation. Further, we show how domains
of the general transcription factor TFIIF affect complex dynamics and control
repressive activity. Together, we reveal how a non-coding RNA can regulate mammalian
gene expression.
acknowledged_ssus:
- _id: LifeSc
- _id: EM-Fac
- _id: PreCl
acknowledgement: "We thank B. Kaczmarek and other members of the Bernecky lab for
helpful discussions. We thank V.-V. Hodirnau for SerialEM data collection and support
with EPU data collection. We thank D. Slade for the wild type TFIIF expression\r\nplasmid.
We thank N. Thompson and R. Burgess for the 8WG16 hybridoma cell line. We thank
C. Plaschka and M. Loose for critical reading of the manuscript. This work was supported
by Austrian Science Fund (FWF) grant P34185. This research was further supported
by the Scientific Service Units (SSU) of IST Austria through resources provided
by the Lab Support Facility (LSF), Electron Microscopy Facility (EMF), Scientific
Computing (SciComp), and the Preclinical Facility (PCF)."
article_processing_charge: No
author:
- first_name: Katarina
full_name: Tluckova, Katarina
id: 4AC7D980-F248-11E8-B48F-1D18A9856A87
last_name: Tluckova
- first_name: Anita P
full_name: Testa Salmazo, Anita P
id: 41F1F098-F248-11E8-B48F-1D18A9856A87
last_name: Testa Salmazo
- first_name: Carrie A
full_name: Bernecky, Carrie A
id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
last_name: Bernecky
orcid: 0000-0003-0893-7036
citation:
ama: Tluckova K, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional
repression by noncoding RNA. doi:10.15479/AT:ISTA:14644
apa: Tluckova, K., Testa Salmazo, A. P., & Bernecky, C. (n.d.). Mechanism of
mammalian transcriptional repression by noncoding RNA. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:14644
chicago: Tluckova, Katarina, Anita P Testa Salmazo, and Carrie Bernecky. “Mechanism
of Mammalian Transcriptional Repression by Noncoding RNA.” Institute of Science
and Technology Austria, n.d. https://doi.org/10.15479/AT:ISTA:14644.
ieee: K. Tluckova, A. P. Testa Salmazo, and C. Bernecky, “Mechanism of mammalian
transcriptional repression by noncoding RNA.” Institute of Science and Technology
Austria.
ista: Tluckova K, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional
repression by noncoding RNA. 10.15479/AT:ISTA:14644.
mla: Tluckova, Katarina, et al. Mechanism of Mammalian Transcriptional Repression
by Noncoding RNA. Institute of Science and Technology Austria, doi:10.15479/AT:ISTA:14644.
short: K. Tluckova, A.P. Testa Salmazo, C. Bernecky, (n.d.).
date_created: 2023-12-04T14:51:00Z
date_published: 2023-12-05T00:00:00Z
date_updated: 2023-12-05T10:37:28Z
day: '05'
ddc:
- '572'
department:
- _id: CaBe
doi: 10.15479/AT:ISTA:14644
file:
- access_level: open_access
checksum: c45608cb97ee36d7b50ba518db8e07b0
content_type: application/pdf
creator: dernst
date_created: 2023-12-05T10:37:02Z
date_updated: 2023-12-05T10:37:02Z
file_id: '14646'
file_name: 2023_Tluckova_etal_REx.pdf
file_size: 4892920
relation: main_file
success: 1
file_date_updated: 2023-12-05T10:37:02Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '12'
oa: 1
oa_version: Submitted Version
project:
- _id: c08a6700-5a5b-11eb-8a69-82a722b2bc30
grant_number: P34185
name: Regulation of mammalian transcription by noncoding RNA
publication_status: submitted
publisher: Institute of Science and Technology Austria
status: public
title: Mechanism of mammalian transcriptional repression by noncoding RNA
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '15061'
abstract:
- lang: eng
text: The actin cytoskeleton, a dynamic network of actin filaments and associated
F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins
are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here
we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2
(EhActn2) with features expected for the common ancestor of Entamoeba and higher
eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-bound EhActn2
reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain.
Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD
for Ca2+, binding of which can only be regulated in the presence of physiological
concentrations of Mg2+. Ca2+ binding triggers an increase in protein multidomain
rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain
cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover
that EhActn2 plays an important role in phagocytic cup formation and might constitute
a new drug target for amoebic dysentery.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: "We thank the staff of the macromolecular crystallography (MX) and
SAXS beamlines at the European Synchrotron Radiation facility, Diamond, and Swiss
Light Source for excellent support, and the Life Sciences Facility of the Institute
of Science and Technology Austria for usage of the rheometer. We thank Life Sciences
editors for editing assistance. EM data were\r\nrecorded at the EM Facility of the
Vienna BioCenter Core Facilities (Austria). Confocal microscopy was carried out
at the Advanced Instrument Research Facility, Jawaharlal Nehru University. K.D.-C.’s
research was supported by the Initial Training Network MUZIC (ITN-MUZIC) (N°238423),
Austrian Science Fund (FWF) Projects I525, I1593, P22276, P19060, and W1221, Laura
Bassi Centre of Optimized Structural Studies (N°253275), a Wellcome Trust Collaborative
Award (201543/Z/16/Z), COST Action BM1405, Vienna Science and Technology Fund (WWTF)
Chemical Biology Project LS17-008, and Christian Doppler Laboratory for High-Content
Structural Biology and Biotechnology. K.Z., J.L.A., C.S., E.A.G., and A.S. were
supported by the University of Vienna, J.K. by a Wellcome Trust Collaborative Award
and by the Centre of Optimized Structural Studies, M.P. by FWF Project I1593, E.d.A.R.
ITN-MUZIC, and FWF Projects I525 and I1593, and T.C.M. and L.C. by FWF Project I
2408-B22. E.A.G. acknowledges the PhD program Structure and Interaction of Biological
Macromolecules. M.B. acknowledges the University Grant Commission, India, for a
senior research fellowship. A.B. acknowledges a JC Bose Fellowship from the Science
Engineering Research Council. "
article_processing_charge: No
article_type: original
author:
- first_name: Nikos
full_name: Pinotsis, Nikos
last_name: Pinotsis
- first_name: Karolina
full_name: Zielinska, Karolina
last_name: Zielinska
- first_name: Mrigya
full_name: Babuta, Mrigya
last_name: Babuta
- first_name: Joan L.
full_name: Arolas, Joan L.
last_name: Arolas
- first_name: Julius
full_name: Kostan, Julius
last_name: Kostan
- first_name: Muhammad Bashir
full_name: Khan, Muhammad Bashir
last_name: Khan
- first_name: Claudia
full_name: Schreiner, Claudia
last_name: Schreiner
- first_name: Anita P
full_name: Testa Salmazo, Anita P
id: 41F1F098-F248-11E8-B48F-1D18A9856A87
last_name: Testa Salmazo
- first_name: Luciano
full_name: Ciccarelli, Luciano
last_name: Ciccarelli
- first_name: Martin
full_name: Puchinger, Martin
last_name: Puchinger
- first_name: Eirini A.
full_name: Gkougkoulia, Eirini A.
last_name: Gkougkoulia
- first_name: Euripedes de Almeida
full_name: Ribeiro, Euripedes de Almeida
last_name: Ribeiro
- first_name: Thomas C.
full_name: Marlovits, Thomas C.
last_name: Marlovits
- first_name: Alok
full_name: Bhattacharya, Alok
last_name: Bhattacharya
- first_name: Kristina
full_name: Djinovic-Carugo, Kristina
last_name: Djinovic-Carugo
citation:
ama: Pinotsis N, Zielinska K, Babuta M, et al. Calcium modulates the domain flexibility
and function of an α-actinin similar to the ancestral α-actinin. Proceedings
of the National Academy of Sciences. 2020;117(36):22101-22112. doi:10.1073/pnas.1917269117
apa: Pinotsis, N., Zielinska, K., Babuta, M., Arolas, J. L., Kostan, J., Khan, M.
B., … Djinovic-Carugo, K. (2020). Calcium modulates the domain flexibility and
function of an α-actinin similar to the ancestral α-actinin. Proceedings of
the National Academy of Sciences. Proceedings of the National Academy of Sciences.
https://doi.org/10.1073/pnas.1917269117
chicago: Pinotsis, Nikos, Karolina Zielinska, Mrigya Babuta, Joan L. Arolas, Julius
Kostan, Muhammad Bashir Khan, Claudia Schreiner, et al. “Calcium Modulates the
Domain Flexibility and Function of an α-Actinin Similar to the Ancestral α-Actinin.”
Proceedings of the National Academy of Sciences. Proceedings of the National
Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1917269117.
ieee: N. Pinotsis et al., “Calcium modulates the domain flexibility and function
of an α-actinin similar to the ancestral α-actinin,” Proceedings of the National
Academy of Sciences, vol. 117, no. 36. Proceedings of the National Academy
of Sciences, pp. 22101–22112, 2020.
ista: Pinotsis N, Zielinska K, Babuta M, Arolas JL, Kostan J, Khan MB, Schreiner
C, Testa Salmazo AP, Ciccarelli L, Puchinger M, Gkougkoulia EA, Ribeiro E de A,
Marlovits TC, Bhattacharya A, Djinovic-Carugo K. 2020. Calcium modulates the domain
flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings
of the National Academy of Sciences. 117(36), 22101–22112.
mla: Pinotsis, Nikos, et al. “Calcium Modulates the Domain Flexibility and Function
of an α-Actinin Similar to the Ancestral α-Actinin.” Proceedings of the National
Academy of Sciences, vol. 117, no. 36, Proceedings of the National Academy
of Sciences, 2020, pp. 22101–12, doi:10.1073/pnas.1917269117.
short: N. Pinotsis, K. Zielinska, M. Babuta, J.L. Arolas, J. Kostan, M.B. Khan,
C. Schreiner, A.P. Testa Salmazo, L. Ciccarelli, M. Puchinger, E.A. Gkougkoulia,
E. de A. Ribeiro, T.C. Marlovits, A. Bhattacharya, K. Djinovic-Carugo, Proceedings
of the National Academy of Sciences 117 (2020) 22101–22112.
date_created: 2024-03-04T10:03:52Z
date_published: 2020-09-08T00:00:00Z
date_updated: 2024-03-04T10:14:44Z
day: '08'
department:
- _id: CaBe
doi: 10.1073/pnas.1917269117
external_id:
pmid:
- '32848067'
intvolume: ' 117'
issue: '36'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.191726911
month: '09'
oa: 1
oa_version: Published Version
page: 22101-22112
pmid: 1
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: Proceedings of the National Academy of Sciences
quality_controlled: '1'
status: public
title: Calcium modulates the domain flexibility and function of an α-actinin similar
to the ancestral α-actinin
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 117
year: '2020'
...