Human angiogenin is a potent cytotoxin in the absence of ribonuclease inhibitor

RNA
Sydney P ThomasRonald T Raines

Abstract

Angiogenin (ANG) is a secretory ribonuclease that promotes the proliferation of endothelial cells, leading to angiogenesis. This function relies on its ribonucleolytic activity, which is low for simple RNA substrates. Upon entry into the cytosol, ANG is sequestered by the ribonuclease inhibitor protein (RNH1). We find that ANG is a potent cytotoxin for RNH1-knockout HeLa cells, belying its inefficiency as a nonspecific catalyst. The toxicity does, however, rely on the ribonucleolytic activity of ANG and a cytosolic localization, which lead to the accumulation of particular tRNA fragments (tRFs), such as tRF-5 Gly-GCC. These up-regulated tRFs are highly cytotoxic at physiological concentrations. Although ANG is well-known for its promotion of cell growth, our results reveal that ANG can also cause cell death.

References

Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·G F HuB L Vallee
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·J Moroianu, J F Riordan
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·G F HuB L Vallee
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·G F Hu
May 26, 2001·Biochemical and Biophysical Research Communications·R LixinD A Jans
Oct 5, 2001·Methods in Enzymology·J F Riordan
Jan 23, 2002·Biochemistry·Peter A LelandRonald T Raines
Dec 17, 2002·Journal of Cell Science·Marcia C Haigis, Ronald T Raines
Feb 1, 2003·Nucleic Acids Research·Marcia C HaigisRonald T Raines
Feb 12, 2004·Bioinformatics·M J L de HoonS Miyano
Jun 8, 2004·Bioinformatics·Alok J Saldanha
Sep 17, 2005·Progress in Nucleic Acid Research and Molecular Biology·Kimberly A DicksonRonald T Raines
Sep 29, 2005·Journal of Molecular Biology·Thomas J RutkoskiRonald T Raines
Jul 18, 2006·Nucleic Acids Research·Oleg KikinParamjeet S Bagga
Aug 22, 2006·Journal of Molecular Biology·Bryan D Smith, Ronald T Raines
Dec 26, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dairín KieranJochen H M Prehn
Apr 1, 2009·The Journal of Cell Biology·Satoshi YamasakiPaul Anderson
Feb 5, 2010·The Journal of Biological Chemistry·Mohamed M EmaraPaul Anderson
May 6, 2011·Bioinformatics·Timothy L Bailey
Jul 27, 2011·PloS One·Fran SupekTomislav Šmuc
Aug 23, 2011·Molecular Cell·Pavel IvanovPaul Anderson
Oct 25, 2011·Journal of Cellular Physiology·Shuping Li, Guo-Fu Hu
Nov 17, 2011·Wiley Interdisciplinary Reviews. RNA·Katsutomo Okamura
Jan 3, 2012·Methods in Enzymology·Jo E LomaxRonald T Raines
Apr 13, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexandra SkorupaJochen H M Prehn
Oct 23, 2012·The Journal of Biological Chemistry·Mridusmita SaikiaMaria Hatzoglou
Nov 28, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Qingrong WangXiaoyong Bao
Jan 24, 2013·Molecular BioSystems·Tzu-Yuan Chao, Ronald T Raines
Jul 27, 2014·The EMBO Journal·Sandra BlancoMichaela Frye
Aug 1, 2014·The Journal of Biological Chemistry·Chelcie H EllerRonald T Raines
Nov 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Pavel IvanovPaul Anderson
May 29, 2015·Nucleic Acids Research·Antonio RuedaMichael Hackenberg
Jul 15, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Junfang DengXiaoyong Bao
Jul 18, 2015·Nucleic Acids Research·Sonia TarazonaAna Conesa
Sep 1, 2015·Nature Methods·Jeremy E Wilusz
Dec 26, 2015·Acta Biochimica Et Biophysica Sinica·Jinghao Sheng, Zhengping Xu

❮ Previous
Next ❯

Citations

Jun 11, 2020·RNA Biology·Sherif RashadKuniyasu Niizuma
Aug 14, 2020·Nucleic Acids Research·Juan Pablo TosarAlfonso Cayota
Oct 5, 2019·The Journal of Biological Chemistry·Zhangli SuAnindya Dutta
Sep 20, 2019·Neural Regeneration Research·Sherif RashadTeiji Tominaga
Dec 19, 2019·Frontiers in Immunology·Giovanni Gotte, Marta Menegazzi
Sep 3, 2019·Frontiers in Pharmacology·Vladimir Alexandrovich MitkevichAlexander Alexander Makarov
Sep 27, 2020·Proceedings of the National Academy of Sciences of the United States of America·Alina IsakovaStephen R Quake
Oct 13, 2020·Journal of Cellular Physiology·Sherif RashadKuniyasu Niizuma
Oct 5, 2018·Molecular Cancer Therapeutics·Trish T HoangRonald T Raines
Jan 9, 2021·Trends in Biochemical Sciences·Juan Pablo TosarAlfonso Cayota
Mar 9, 2021·Clinical, Cosmetic and Investigational Dermatology·Natalia V YurinaAlexey V Purtov
Sep 14, 2020·DNA Repair·Cathrine Broberg Vågbø, Geir Slupphaug
Apr 4, 2021·International Journal of Molecular Sciences·Marisa PereiraAna R Soares
Jul 9, 2021·Frontiers in Neurology·Marina Gabriel-SalazarAnna Rosell

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.