24 research outputs found
The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition
Nearly half of the human genome is made of transposable elements (TEs) whose activity
continues to impact its structure and function. Among them, Long INterspersed Element class
1 (LINE-1 or L1) elements are the only autonomously active TEs in humans. L1s are expressed
and mobilized in different cancers, generating mutagenic insertions that could affect tumor
malignancy. Tumor suppressor microRNAs are âŒ22nt RNAs that post-transcriptionally regulate
oncogene expression and are frequently downregulated in cancer. Here we explore
whether they also influence L1 mobilization. We show that downregulation of let-7 correlates
with accumulation of L1 insertions in human lung cancer. Furthermore, we demonstrate that
let-7 binds to the L1 mRNA and impairs the translation of the second L1-encoded protein,
ORF2p, reducing its mobilization. Overall, our data reveals that let-7, one of the most relevant
microRNAs, maintains somatic genome integrity by restricting L1 retrotransposition.European Research Council (ERC)
ERC-2009-StG 243312French National Research Agency (ANR)
ANR-11-LABX-0028-01
ANR-15-IDEX-01Centre National de la Recherche Scientifique (CNRS)
3546University Hospital Federation (FHU) OncoAgeMINECO
PEJ-2014-A-31985
SAF2015-71589-PMINECO by European Regional Development Fund
SAF2015-71589-PSpanish Government
RYC-2016-21395Career Integration Grant-Marie Curie
FP7-PEOPLE-2011-CIG-30381
Observation of a kilogram-scale oscillator near its quantum ground state
We introduce a novel cooling technique capable of approaching the quantum ground state of a kilogram-scale systemâan interferometric gravitational wave detector. The detectors of the Laser Interferometer Gravitational-wave Observatory (LIGO) operate within a factor of 10 of the standard quantum limit (SQL), providing a displacement sensitivity of 10â18 m in a 100 Hz band centered on 150 Hz. With a new feedback strategy, we dynamically shift the resonant frequency of a 2.7 kg pendulum mode to lie within this optimal band, where its effective temperature falls as low as 1.4 ÎŒK, and its occupation number reaches about 200 quanta. This work shows how the exquisite sensitivity necessary to detect gravitational waves can be made available to probe the validity of quantum mechanics on an enormous mass scale