scholarly journals The RNA-binding protein Sam68 is a multifunctional player in human cancer

2011 ◽  
Vol 18 (4) ◽  
pp. R91-R102 ◽  
Author(s):  
Pamela Bielli ◽  
Roberta Busà ◽  
Maria Paola Paronetto ◽  
Claudio Sette

Src associated in mitosis, of 68 kDa (Sam68) is a KH domain RNA-binding protein that belongs to the signal transduction and activation of RNA family. Although ubiquitously expressed, Sam68 plays very specialized roles in different cellular environments. In most cells, Sam68 resides in the nucleus and is involved in several steps of mRNA processing, from transcription, to alternative splicing, to nuclear export. In addition, Sam68 translocates to the cytoplasm upon cell stimulation, cell cycle transitions or viral infections, where it takes part to signaling complexes and associates with the mRNA translation machinery. Recent evidence has linked Sam68 function to the onset and progression of endocrine tumors, such as prostate and breast carcinomas. Notably, all the biochemical activities reported for Sam68 seem to be implicated in carcinogenesis. Herein, we review the recent advancement in the knowledge of Sam68 function and regulation and discuss it in the frame of its participation to neoplastic transformation and tumor progression.

2017 ◽  
Vol 104 (3) ◽  
pp. 428-448 ◽  
Author(s):  
Ryosuke Satoh ◽  
Yasuhiro Matsumura ◽  
Akitomo Tanaka ◽  
Makoto Takada ◽  
Yuna Ito ◽  
...  

2018 ◽  
Vol 5 (12) ◽  
pp. 180336
Author(s):  
Michele Sanguanini ◽  
Antonino Cattaneo

The regulation of mRNA translation at the level of the synapse is believed to be fundamental in memory and learning at the cellular level. The family of cytoplasmic polyadenylation element binding (CPEB) proteins emerged as an important RNA-binding protein family during development and in adult neurons. Drosophila Orb2 (homologue of mouse CPEB3 protein and of the neural isoform of Aplysia CPEB) has been found to be involved in the translation of plasticity-dependent mRNAs and has been associated with long-term memory. Orb2 protein presents two main isoforms, Orb2A and Orb2B, which form an activity-induced amyloid-like functional aggregate, thought to be the translation-inducing state of the RNA-binding protein. Here we present a first two-states continuous differential model for Orb2A–Orb2B aggregation. This model provides new working hypotheses for studying the role of prion-like CPEB proteins in long-term synaptic plasticity. Moreover, this model can be used as a first step to integrate translation- and protein aggregation-dependent phenomena in synaptic facilitation rules.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Cai-Rong Yang ◽  
Gabriel Rajkovic ◽  
Enrico Maria Daldello ◽  
Xuan G. Luong ◽  
Jing Chen ◽  
...  

2020 ◽  
Vol 295 (42) ◽  
pp. 14291-14304
Author(s):  
Kathrin Bajak ◽  
Kevin Leiss ◽  
Christine Clayton ◽  
Esteban Erben

In Trypanosoma brucei and related kinetoplastids, gene expression regulation occurs mostly posttranscriptionally. Consequently, RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Yet, the roles of many RNA-binding proteins are not understood. Our previous research identified the RNA-binding protein ZC3H5 as possibly involved in gene repression, but its role in controlling gene expression was unknown. We here show that ZC3H5 is an essential cytoplasmic RNA-binding protein. RNAi targeting ZC3H5 causes accumulation of precytokinetic cells followed by rapid cell death. Affinity purification and pairwise yeast two-hybrid analysis suggest that ZC3H5 forms a complex with three other proteins, encoded by genes Tb927.11.4900, Tb927.8.1500, and Tb927.7.3040. RNA immunoprecipitation revealed that ZC3H5 is preferentially associated with poorly translated, low-stability mRNAs, the 5′-untranslated regions and coding regions of which are enriched in the motif (U/A)UAG(U/A). As previously found in high-throughput analyses, artificial tethering of ZC3H5 to a reporter mRNA or other complex components repressed reporter expression. However, depletion of ZC3H5 in vivo caused only very minor decreases in a few targets, marked increases in the abundances of very stable mRNAs, an increase in monosomes at the expense of large polysomes, and appearance of “halfmer” disomes containing two 80S subunits and one 40S subunit. We speculate that the ZC3H5 complex might be implicated in quality control during the translation of suboptimal open reading frames.


Science ◽  
2016 ◽  
Vol 353 (6307) ◽  
pp. 1549-1552 ◽  
Author(s):  
A. Kanakkanthara ◽  
K. B. Jeganathan ◽  
J. F. Limzerwala ◽  
D. J. Baker ◽  
M. Hamada ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126978 ◽  
Author(s):  
Louise F. Thatcher ◽  
Lars G. Kamphuis ◽  
James K. Hane ◽  
Luis Oñate-Sánchez ◽  
Karam B. Singh

2019 ◽  
Vol 294 (52) ◽  
pp. 19889-19895 ◽  
Author(s):  
Phillip J. Hsu ◽  
Hailing Shi ◽  
Allen C. Zhu ◽  
Zhike Lu ◽  
Nimrod Miller ◽  
...  

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Mehrpouya B. Mobin ◽  
Stefanie Gerstberger ◽  
Daniel Teupser ◽  
Benedetta Campana ◽  
Klaus Charisse ◽  
...  

2014 ◽  
Vol 15 (1) ◽  
pp. R4 ◽  
Author(s):  
Linan Chen ◽  
Jason G Dumelie ◽  
Xiao Li ◽  
Matthew HK Cheng ◽  
Zhiyong Yang ◽  
...  

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