Back

Role for Merlin/NF2 in transcription elongation through interaction with the PAF complex

Roehrigh, A. E.; Klupsch, K.; Oses-Prieto, J. A.; Chaib, S.; Henderson, S.; Emmett, W.; Young, L. C.; Surinova, S.; Blees, A.; Pfeiffer, A.; Tijani, M.; Brunk, F.; Hartig, N.; Munoz-Alegre, M.; Hergovich, A.; Jennings, B.; Burlingame, A. L.; Rodriguez-Viciana, P.

2019-07-28 cancer biology
10.1101/717769 bioRxiv
Show abstract

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing events and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions at the cell cortex and nucleus and is a key mediator of contact inhibition. Here we provide a direct link between nuclear Merlin and transcription elongation controlled by cell-cell adhesion. Merlin interacts with the PAFC in a cell density-dependent manner and tumour-derived inactivating mutations in both Merlin and CDC73 mutually disrupt their interaction. Growth suppression by Merlin requires CDC73 and Merlin regulates PAFC association with chromatin in a subset of genes. We also identify by CDC73 affinity-proteomics a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, nuclear Merlin is part of a tumour suppressor network which coordinates postinitiation steps of the transcription cycle of genes mediating in contact inhibition.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

1
eLife
● 5828 papers in training set
Top 2%
21.4%
Similar papers in this journal
2
Cell Reports
○ 1498 papers in training set
Top 0.7%
14.7%
Similar papers in this journal
3
The EMBO Journal
○ 309 papers in training set
Top 0.3%
7.7%
Similar papers in this journal
4
Nature Communications
○ 5641 papers in training set
Top 24%
6.6%
Similar papers in this journal
50% of probability mass above
5
Life Science Alliance
● 285 papers in training set
Top 0.5%
5.3%
Similar papers in this journal
6
Journal of Cell Biology
● 392 papers in training set
Top 1%
4.7%
7
Journal of Cell Science
● 393 papers in training set
Top 1%
4.7%
8
Molecular Cell
○ 350 papers in training set
Top 1%
4.3%
9
EMBO Reports
○ 263 papers in training set
Top 2%
3.0%
10
Genes & Development
● 90 papers in training set
Top 0.5%
2.6%
11
Molecular Cancer Research
● 49 papers in training set
Top 0.5%
2.4%
12
Molecular and Cellular Biology
○ 47 papers in training set
Top 0.3%
2.3%
13
Oncogene
○ 85 papers in training set
Top 0.9%
1.9%
14
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 31%
1.5%
15
PLOS Genetics
● 862 papers in training set
Top 8%
1.4%
16
iScience
○ 1154 papers in training set
Top 31%
1.0%
17
Science Advances
● 1243 papers in training set
Top 29%
1.0%
18
Developmental Cell
○ 196 papers in training set
Top 4%
1.0%
19
Nucleic Acids Research
◐ 1281 papers in training set
Top 14%
0.8%
20
Molecular Systems Biology
○ 162 papers in training set
Top 3%
0.8%
21
Journal of Biological Chemistry
○ 690 papers in training set
Top 10%
0.8%
22
Genome Research
● 468 papers in training set
Top 7%
0.6%
23
Open Biology
● 106 papers in training set
Top 3%
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.