10 research outputs found
Evidence for reassociation of RNA-binding proteins after cell lysis: Implications for the interpretation of immunoprecipitation analyses
Immuno- and other affinity-purification approaches are commonly used to characterize the composition of ribonucleoprotein complexes. While associations detected by these procedures are often interpreted as reflecting in vivo interactions, it is also possible that they arise from reassociation of molecules after cell lysis. Here we used an experimental approach that allowed us to distinguish between these possibilities. Surprisingly, we show that the association of the RNA-binding protein HuR with its target mRNA, c-fos, as detected by co-immunoprecipitation, results largely from reassociation of molecules subsequent to cell lysis. The existence of such postlysis reassortments thus demonstrates that co-immunoprecipitation does not always recapitulate the in vivo state of ribonucleoprotein complexes
Obesity, metabolic syndrome, and cancer: pathophysiological and therapeutic associations
Overweight, obesity, and metabolic syndrome (MetS) have become epidemic
conditions affecting 39%, 13%, and 20% of the population
respectively. The aim of this article is to review the literature on the
association of obesity and MetS with the risk of cancer. We also explore
the effect of lifestyle modifications, such as diet, physical activity,
and antidiabetic medications, on cancer incidence. Increased body mass
index (BMI) has been associated with a multitude of site-specific
cancers, reaching relative risk (RR) 1.54 [95% confidence interval
(CI) 1.47-1.61] per 5 unit increase for endometrial cancer, as well as
with overall cancer risk (RR 1.03, 95% CI 1.02-1.05). Central adiposity
measured by waist circumference or waist-to-hip ratio has been suggested
as a stronger predictor than BMI for several cancers, such as colorectal
cancer. Metabolic Syndrome has been consistently and positively
associated with the risk of very common cancers like colorectal (RR
1.34, 95% CI 1.24-1.44), endometrial (RR 1.62, 95% CI 1.26-2.07) and
postmenopausal breast cancer (RR 2.01, 95% CI 1.55-2.60). Hyperglycemia
and subsequently T2DM have been also shown to increase the risk of
cancer. Nevertheless, these risk factors are modifiable and therefore
implementing lifestyle modifications could prevent an important number
of cancer cases. Adherence to cancer prevention guidelines, including
maintaining a healthy weight, having regular physical exercise (RR
0.58-0.90 for different cite specific cancers) and following a healthy
dietary pattern (RR 0.74-0.94 for different cite specific cancers) have
a protective effect on the risk of cancer. The strength of this review
is the presentation of the best evidence, as the data derive mainly from
meta-analyses. Public health policies should focus on the modification
of risk factors and future research is needed to reveal the
pathophysiological links between these risk factors and cancer to
develop more efficient prevention and treatment strategies
The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions
International audienceRNA localization and local translation are important for numerous cellular functions. In mammals, a class of mRNAs localize to cytoplasmic protrusions in an APC-dependent manner, with roles during cell migration. Here, we investigated this localization mechanism. We found that the KIF1C motor interacts with APC-dependent mRNAs and is required for their localization. Live cell imaging revealed rapid, active transport of single mRNAs over long distances that requires both microtubules and KIF1C. Two color imaging directly revealed single mRNAs transported by single KIF1C motors, with the 3’UTR being sufficient to trigger KIF1C-dependent RNA transport and localization. Moreover, KIF1C remained associated with peripheral, multimeric RNA clusters and was required for their formation. These results reveal a widespread RNA transport pathway in mammalian cells, in which the KIF1C motor has a dual role in transporting RNAs and clustering them within cytoplasmic protrusions. Interestingly, KIF1C also transports its own mRNA suggesting a possible feedback loop acting at the level of mRNA transport