scholarly journals Fibrillarin Ribonuclease Activity is Dependent on the GAR Domain and Modulated by Phospholipids

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1143 ◽  
Author(s):  
Francisco Guillen-Chable ◽  
Ulises Rodríguez Corona ◽  
Alejandro Pereira-Santana ◽  
Andrea Bayona ◽  
Luis Carlos Rodríguez-Zapata ◽  
...  

Fibrillarin is a highly conserved nucleolar methyltransferase responsible for ribosomal RNA methylation across evolution from Archaea to humans. It has been reported that fibrillarin is involved in the methylation of histone H2A in nucleoli and other processes, including viral progression, cellular stress, nuclear shape, and cell cycle progression. We show that fibrillarin has an additional activity as a ribonuclease. The activity is affected by phosphoinositides and phosphatidic acid and insensitive to ribonuclease inhibitors. Furthermore, the presence of phosphatidic acid releases the fibrillarin-U3 snoRNA complex. We show that the ribonuclease activity localizes to the GAR (glycine/arginine-rich) domain conserved in a small group of RNA interacting proteins. The introduction of the GAR domain occurred in evolution in the transition from archaea to eukaryotic cells. The interaction of this domain with phospholipids may allow a phase separation of this protein in nucleoli.

2021 ◽  
Author(s):  
Roy Baas ◽  
Fenna J. van der Wal ◽  
Onno B. Bleijerveld ◽  
Haico van Attikum ◽  
Titia K. Sixma

AbstractBRCA1-associated protein 1 (BAP1) is a tumor suppressor and its loss can result in mesothelioma, uveal and cutaneous melanoma, clear cell renal cell carcinoma and bladder cancer. BAP1 is a deubiquitinating enzyme of the UCH class that has been implicated in various cellular processes like cell growth, cell cycle progression, ferroptosis and ER metabolic stress response. ASXL proteins activate BAP1 by forming the polycomb repressive deubiquitinase (PR-DUB) complex which acts on H2AK119ub1. Besides the ASXL proteins, BAP1 is known to interact with an established set of additional proteins.Here, we identify novel BAP1 interacting proteins in the cytoplasm by expressing GFP-tagged BAP1 in an endogenous BAP1 deficient cell line using affinity purification followed by mass spectrometry (AP-MS) analysis. Among these novel interacting proteins are Histone acetyltransferase 1 (HAT1) and all subunits of the heptameric coat protein complex I (COPI) that is involved in vesicle formation and protein cargo binding and sorting. We validate that the HAT1 and COPI interactions occur at endogenous levels but find that this interaction with COPI is not mediated through the C-terminal KxKxx cargo sorting signals of the COPI complex.


PLoS Genetics ◽  
2008 ◽  
Vol 4 (8) ◽  
pp. e1000171 ◽  
Author(s):  
Norimasa Iwanami ◽  
Tomokazu Higuchi ◽  
Yumi Sasano ◽  
Toshinobu Fujiwara ◽  
Vu Q. Hoa ◽  
...  

2013 ◽  
Vol 6 (S1) ◽  
Author(s):  
Jiadong Wang ◽  
Justin Wai Chung Leung ◽  
Zihua Gong ◽  
Lin Feng ◽  
Xiaobing Shi ◽  
...  

2012 ◽  
Vol 5 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Toshiaki Kawakami ◽  
Tomoaki Ando ◽  
Yuko Kawakami

Histamine-releasing factor (HRF), also termed translationally controlled tumor protein (TCTP) and fortilin, is a highly conserved, multi-functional protein. This protein within a cell plays a critical role in the fundamental processes of cell-cycle progression, proliferation, survival, and malignant transformation. The same protein, despite the lack of signal sequence, is secreted through a nonclassical secretory pathway. The secreted protein usually termed HRF can activate IgE-primed basophils and mast cells, and works as a B cell growth factor and a chemoattractant for eosinophils. This structurally well-characterized protein interacts with many proteins to perform its intracellular and extracellular functions. This review summarizes recent studies of HRF/TCTP-interacting proteins as a major driving force to decipher its functions.


2012 ◽  
Vol 288 (5) ◽  
pp. 3174-3183 ◽  
Author(s):  
Jiadong Wang ◽  
Justin Wai-chung Leung ◽  
Zihua Gong ◽  
Lin Feng ◽  
Xiaobing Shi ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257688
Author(s):  
Roy Baas ◽  
Fenna J. van der Wal ◽  
Onno B. Bleijerveld ◽  
Haico van Attikum ◽  
Titia K. Sixma

BRCA1-associated protein 1 (BAP1) is a tumor suppressor and its loss can result in mesothelioma, uveal and cutaneous melanoma, clear cell renal cell carcinoma and bladder cancer. BAP1 is a deubiquitinating enzyme of the UCH class that has been implicated in various cellular processes like cell growth, cell cycle progression, ferroptosis, DNA damage response and ER metabolic stress response. ASXL proteins activate BAP1 by forming the polycomb repressive deubiquitinase (PR-DUB) complex which acts on H2AK119ub1. Besides the ASXL proteins, BAP1 is known to interact with an established set of additional proteins. Here, we identify novel BAP1 interacting proteins in the cytoplasm by expressing GFP-tagged BAP1 in an endogenous BAP1 deficient cell line using affinity purification followed by mass spectrometry (AP-MS) analysis. Among these novel interacting proteins are Histone acetyltransferase 1 (HAT1) and all subunits of the heptameric coat protein complex I (COPI) that is involved in vesicle formation and protein cargo binding and sorting. We validate that the HAT1 and COPI interactions occur at endogenous levels but find that this interaction with COPI is not mediated through the C-terminal KxKxx cargo sorting signals of the COPI complex.


2006 ◽  
Vol 26 (2) ◽  
pp. 489-501 ◽  
Author(s):  
Namrita Dhillon ◽  
Masaya Oki ◽  
Shawn J. Szyjka ◽  
Oscar M. Aparicio ◽  
Rohinton T. Kamakaka

ABSTRACT Histone H2A variants are highly conserved proteins found ubiquitously in nature and thought to perform specialized functions in the cell. Studies in yeast on the histone H2A variant H2A.Z have shown a role for this protein in transcription as well as chromosome segregation. Our studies have focused on understanding the role of H2A.Z during cell cycle progression. We found that htz1Δ cells were delayed in DNA replication and progression through the cell cycle. Furthermore, cells lacking H2A.Z required the S-phase checkpoint pathway for survival. We also found that H2A.Z localized to the promoters of cyclin genes, and cells lacking H2A.Z were delayed in the induction of these cyclin genes. Several different models are proposed to explain these observations.


2009 ◽  
Vol 17 (4) ◽  
pp. 18-21 ◽  
Author(s):  
Jack Coleman ◽  
Hilary Cox ◽  
Zaiguo Li ◽  
Praveen Pande ◽  
Dee Shen ◽  
...  

The nucleolus represents a highly dynamic nuclear domain arising from an equilibrium between the level of ribosomal RNA synthesis and the efficiency of ribosomal RNA processing [1, 2]. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now demonstrate that it has additional functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response, and biogenesis of multiple ribonucleoprotein particles. Ribosome biogenesis is regulated throughout interphase and ceases during mitosis (Figure 1). Thus, there is a direct relationship between cell growth and nucleolar activities. Nucleoli are well known to be dramatically modified in cancer cells. Additionally, a large number of key proteins from both DNA- and RNA-containing viruses are localized in the nucleolus, including the human immunodeficiency virus (HIV)-1 Rev and Tat proteins. Targeting of viral proteins to the nucleolus not only facilitates virus replication, but may also be required for pathogenic processes. The nucleolus can also be considered a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm through its disruption.


Sign in / Sign up

Export Citation Format

Share Document