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Open accessJournalISSN: 2050-084X

eLife

About: eLife is an academic journal. The journal publishes majorly in the area(s): Population & Stem cell. It has an ISSN identifier of 2050-084X. It is also open access. Over the lifetime, 14894 publication(s) have been published receiving 420624 citation(s).

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Topics: Population, Stem cell, Chromatin ...read more
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Open accessJournal ArticleDOI: 10.7554/ELIFE.05005
Vikram Agarwal1, George W. Bell1, Jin Wu Nam2, Jin Wu Nam1  +1 moreInstitutions (2)
12 Aug 2015-eLife
Abstract: Proteins are built by using the information contained in molecules of messenger RNA (mRNA). Cells have several ways of controlling the amounts of different proteins they make. For example, a so-called ‘microRNA’ molecule can bind to an mRNA molecule to cause it to be more rapidly degraded and less efficiently used, thereby reducing the amount of protein built from that mRNA. Indeed, microRNAs are thought to help control the amount of protein made from most human genes, and biologists are working to predict the amount of control imparted by each microRNA on each of its mRNA targets. All RNA molecules are made up of a sequence of bases, each commonly known by a single letter—‘A’, ‘U’, ‘C’ or ‘G’. These bases can each pair up with one specific other base—‘A’ pairs with ‘U’, and ‘C’ pairs with ‘G’. To direct the repression of an mRNA molecule, a region of the microRNA known as a ‘seed’ binds to a complementary sequence in the target mRNA. ‘Canonical sites’ are regions in the mRNA that contain the exact sequence of partner bases for the bases in the microRNA seed. Some canonical sites are more effective at mRNA control than others. ‘Non-canonical sites’ also exist in which the pairing between the microRNA seed and mRNA does not completely match. Previous work has suggested that many non-canonical sites can also control mRNA degradation and usage. Agarwal et al. first used large experimental datasets from many sources to investigate microRNA activity in more detail. As expected, when mRNAs had canonical sites that matched the microRNA, mRNA levels and usage tended to drop. However, no effect was observed when the mRNAs only had recently identified non-canonical sites. This suggests that microRNAs primarily bind to canonical sites to control protein production. Based on these results, Agarwal et al. further developed a statistical model that predicts the effects of microRNAs binding to canonical sites. The updated model considers 14 different features of the microRNA, microRNA site, or mRNA—including the mRNA sequence around the site—to predict which sites within mRNAs are most effectively targeted by microRNAs. Tests showed that Agarwal et al.'s model was as good as experimental approaches at identifying the effective target sites, and was better than existing computational models. The model has been used to power the latest version of a freely available resource called TargetScan, and so could prove a valuable resource for researchers investigating the many important roles of microRNAs in controlling protein production.

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Topics: Lin-4 microRNA precursor (60%), PAR-CLIP (53%), microRNA (51%)

3,955 Citations


Open accessJournal ArticleDOI: 10.7554/ELIFE.42166
09 Nov 2018-eLife
Abstract: Here, we describe the third major release of RELION. CPU-based vector acceleration has been added in addition to GPU support, which provides flexibility in use of resources and avoids memory limitations. Reference-free autopicking with Laplacian-of-Gaussian filtering and execution of jobs from python allows non-interactive processing during acquisition, including 2D-classification, de novo model generation and 3D-classification. Per-particle refinement of CTF parameters and correction of estimated beam tilt provides higher resolution reconstructions when particles are at different heights in the ice, and/or coma-free alignment has not been optimal. Ewald sphere curvature correction improves resolution for large particles. We illustrate these developments with publicly available data sets: together with a Bayesian approach to beam-induced motion correction it leads to resolution improvements of 0.2-0.7 A compared to previous RELION versions.

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2,115 Citations


Open accessJournal ArticleDOI: 10.7554/ELIFE.00471
Martin Jinek1, Alexandra East1, Aaron T. Cheng1, Steven Lin1  +2 moreInstitutions (1)
29 Jan 2013-eLife
Abstract: Type II CRISPR immune systems in bacteria use a dual RNA-guided DNA endonuclease, Cas9, to cleave foreign DNA at specific sites. We show here that Cas9 assembles with hybrid guide RNAs in human cells and can induce the formation of double-strand DNA breaks (DSBs) at a site complementary to the guide RNA sequence in genomic DNA. This cleavage activity requires both Cas9 and the complementary binding of the guide RNA. Experiments using extracts from transfected cells show that RNA expression and/or assembly into Cas9 is the limiting factor for Cas9-mediated DNA cleavage. In addition, we find that extension of the RNA sequence at the 3' end enhances DNA targeting activity in vivo. These results show that RNA-programmed genome editing is a facile strategy for introducing site-specific genetic changes in human cells.DOI:http://dx.doi.org/10.7554/eLife.00471.001.

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Topics: Cas9 (70%), Base pair (66%), RNA editing (66%) ...read more

1,890 Citations


Open accessJournal ArticleDOI: 10.7554/ELIFE.00049
Huan Yan1, Guocai Zhong, Guangwei Xu, Wenhui He2  +16 moreInstitutions (2)
13 Nov 2012-eLife
Abstract: Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157-165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.

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Topics: Hepatitis D virus (62%), SLC10A1 (59%), Hepatitis B virus (58%) ...read more

1,373 Citations


Open accessJournal ArticleDOI: 10.7554/ELIFE.13410
26 Jul 2016-eLife
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

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Topics: Population (52%)

1,270 Citations


Performance
Metrics
No. of papers from the Journal in previous years
YearPapers
20211,931
20202,452
20192,160
20181,842
20171,951
20161,703

Top Attributes

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Journal's top 5 most impactful authors

Peter Walter

22 papers, 839 citations

Frank Jülicher

13 papers, 568 citations

Chris Q. Doe

11 papers, 154 citations

Didier Y.R. Stainier

11 papers, 121 citations

Axel T. Brunger

10 papers, 275 citations

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