Back

Ribosome changes elicit non-canonical translation for chemosurvival in G0 leukemic cells

Datta, C.; Truesdell, S. S.; Bukhari, S. I.; Ngue, H.; Buchanan, B.; Wu, K. Q.; Le Tonqueze, O.; Lee, S.; Granovetter, M.; Boukhali, M.; Kreuzer, J.; Haas, W.; Vasudevan, S.

2021-12-08 molecular biology
10.1101/2021.12.07.471635 bioRxiv
Show abstract

Quiescent leukemic cells survive chemotherapy, with translation changes. Our data reveal that FXR1, a protein amplified in several aggressive cancers, increases in quiescent and chemo- treated leukemic cells, and promotes chemosurvival. This suggests undiscovered roles for this RNA- and ribosome-associated protein in chemosurvival. FXR1 depletion decreases translation and ribosome subunits, with altered rRNAs, snoRNAs, and ribosomal proteins (RPs). We find that FXR1 binds factors that promote ribosome gene transcription and bind snoRNAs. Ribosome changes increased in FXR1-overexpressing cells, including increased snoRNAs and RPLP0/uL10, activate eIF2 kinases. Accordingly, phospho-eIF2 increases, enabling non- canonical translation of survival and immune regulators in FXR1-overexpressing cells. Overriding these with inhibitors reduces chemosurvival. Thus, increased FXR1 in quiescent or chemo-treated leukemic cells, alters ribosomes that trigger stress signals to re-direct translation for chemosurvival. One Sentence SummaryFXR1 alters ribosomes in G0, which induce stress signals to elicit noncanonical translation for AML drug and immune survival.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

1
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 3%
10.6%
Similar papers in this journal
2
Cell Reports
○ 1498 papers in training set
Top 2%
9.7%
Similar papers in this journal
3
Nucleic Acids Research
◐ 1281 papers in training set
Top 2%
9.7%
Similar papers in this journal
4
Journal of Biological Chemistry
○ 690 papers in training set
Top 1%
6.7%
Similar papers in this journal
5
RNA
● 189 papers in training set
Top 0.3%
6.7%
Similar papers in this journal
6
NAR Cancer
◐ 37 papers in training set
Top 0.1%
5.5%
7
eLife
● 5828 papers in training set
Top 22%
5.5%
50% of probability mass above
8
Molecular and Cellular Biology
○ 47 papers in training set
Top 0.1%
4.3%
9
PLOS Genetics
● 862 papers in training set
Top 4%
3.4%
10
Science Advances
● 1243 papers in training set
Top 11%
3.2%
11
Nature Communications
○ 5641 papers in training set
Top 35%
3.2%
12
Molecular Cell
○ 350 papers in training set
Top 2%
2.4%
13
RNA Biology
○ 78 papers in training set
Top 0.6%
1.7%
14
iScience
○ 1154 papers in training set
Top 21%
1.5%
15
Science Signaling
● 65 papers in training set
Top 0.8%
1.4%
16
PLOS Pathogens
● 820 papers in training set
Top 7%
1.1%
17
The EMBO Journal
○ 309 papers in training set
Top 5%
1.0%
18
PLOS ONE
● 5266 papers in training set
Top 55%
1.0%
19
Genome Biology
○ 637 papers in training set
Top 8%
1.0%
20
EMBO Reports
○ 263 papers in training set
Top 7%
0.8%
21
mBio
● 833 papers in training set
Top 11%
0.8%
22
Scientific Reports
○ 3612 papers in training set
Top 73%
0.8%
23
Molecular Cancer Research
● 49 papers in training set
Top 1%
0.8%
24
Cell Genomics
○ 172 papers in training set
Top 4%
0.8%
25
Journal of Clinical Investigation
● 179 papers in training set
Top 6%
0.8%
26
Oncogene
○ 85 papers in training set
Top 2%
0.6%
27
Science Translational Medicine
● 127 papers in training set
Top 4%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.