METTL13 methylation of eEF1A increases translational output to promote tumorigenesis

Increased protein synthesis plays an etiologic role in diverse cancers. Here, we demonstrate that METTL13 (methyltransferase-like 13) dimethylation of eEF1A (eukaryotic elongation factor 1A) lysine 55 (eEF1AK55me2) is utilized by Ras-driven cancers to increase translational output and promote tumorigenesis in vivo. METTL13-catalyzed eEF1A methylation increases eEF1A's intrinsic GTPase activity in vitro and protein production in cells. METTL13 and eEF1AK55me2 levels are upregulated in cancer and negatively correlate with pancreatic and lung cancer patient survival. METTL13 deletion and eEF1AK55me2 loss dramatically reduce Ras-driven neoplastic growth in mouse models and in patient-derived xenografts (PDXs) from primary pancreatic and lung tumors. Finally, METTL13 depletion renders PDX tumors hypersensitive to drugs that target growth-signaling pathways. Together, our work uncovers a mechanism by which lethal cancers become dependent on the METTL13-eEF1AK55me2 axis to meet their elevated protein synthesis requirement and suggests that METTL13 inhibition may constitute a targetable vulnerability of tumors driven by aberrant Ras signaling.We thank Pal Falnes, Jerry Pelletier, and Julien Sage for helpful discussion, Lauren Brown and William Devine for SDS-1-021, and members of the Gozani and Mazur laboratories for critical reading of the manuscript. This work was supported in part by grants from the NIH to S.M.C. (K99CA190803), M.P.K. (5K08CA218690-02), J.A.P. (R35GM118173), M.C.B. (1DP2HD084069-01), J.S. (1R35GM119721), I.T. (R01CA202021), P.K.M. (R00CA197816, P50CA070907, and P30CA016672), and O.G. (R01GM079641). J.E.E. received support from Stanford ChEM-H, and A.M. was supported by the MD Anderson Moonshot Program. I.T. is a Junior 2 Research Scholar of the Fonds de Recherche du Quebec - Sante (FRQ-S). P.K.M. is supported by the Neuroendocrine Tumor Research Foundation and American Association for Cancer Research and is the Andrew Sabin Family Foundation Scientist and CPRIT scholar (RR160078). S.H. is supported by a Deutsche Forschungsgemeinschaft Postdoctoral Fellowship. J.W.F. is supported by 5T32GM007276. (K99CA190803 - NIH; 5K08CA218690-02 - NIH; R35GM118173 - NIH; 1DP2HD084069-01 - NIH; 1R35GM119721 - NIH; R01CA202021 - NIH; R00CA197816 - NIH; P50CA070907 - NIH; P30CA016672 - NIH; R01GM079641 - NIH; Stanford ChEM-H; MD Anderson Moonshot Program; Neuroendocrine Tumor Research Foundation; American Association for Cancer Research; Deutsche Forschungsgemeinschaft Postdoctoral Fellowship; 5T32GM007276)Supporting documentationAccepted manuscrip

Web analytics, social media, and the journalistic doxa : the impact of audience feedback on the evolving gatekeeping process

New communication technologies have allowed not only new ways in which the audience interacts with the news but also new ways in which journalists can monitor online audience behavior. Through new audience information systems--web analytics and social media--the influence of the audience on the news construction process is increasing. This occurs as the journalistic field tries to survive a shrinking audience for news. In this mixed methods research, I argue that how journalists conceive of the audience as a form of capital influences the extent to which journalists integrate audience feedback from analytics and social media in their news work. I developed this theoretical framework through case studies of three online newsrooms that included a total of 150 hours of observations and 30 respondent interviews. I subsequently tested the theoretical framework refined through my qualitative analysis using structural equation modeling (SEM) based on survey data collected from 276 online editors. The findings showed a process of negotiation--between providing what audiences need and what they want, between editorial autonomy and audience influence, and between individual agency and organizational constraints--that should clarify how we understand gatekeeping in this age of a knowable and quantifiable audience.Includes bibliographical references (pages 205-223)

Journalism at the Periphery

The increasing influence of actors who might not fit into traditional definitions of a journalist but are taking part in processes that produce journalism has attracted scholarly attention. They have been called interlopers, strangers, new entrants, peripheral, and emergent actors, among others. As journalism scholars grapple with how to refer to these actors, it is important to reflect on the assumptions that underlie emerging labels. These include: 1) what journalistic tasks are involved; 2) how and why these journalistic tasks are performed; 3) who is making the definition; and 4) where and when these actors are located. However, journalism being the centre of our investigation should not automatically assume that it is at the centre of social life. So, it might also be that for the technological field, journalism is at the periphery; that for these technology-oriented actors whose influence across fields is increasing, journalists and what they do are at the periphery. For a field that supposedly plays an important role in public life, this has important implications

HELPING STRUGGLING READERS TO READ: THE IMPACT OF THE CARE FOR THE NON-READERS (CRN) PROGRAM ON FILIPINO PUPILS’ READING PROFICIENCY

This study was conducted to determine the impact of the Care for the Non-Readers Program on the reading performance of struggling readers in all elementary schools of Dumingag II District, Dumingag, Zamboanga del Sur, Mindanao, Philippines during the School Year 2016-2017. Fifty teachers and 465 parents were selected as respondents of the study. It made use of the descriptive comparative method of research with the questionnaire-checklist as data-gathering instrument. Both the descriptive and inferential statistics were used in the analysis and interpretation of data. The findings of the study revealed that both teachers and parents considered the Care for the Non-Readers Program as “Very Effective” in improving the reading performance of pupils. “Fuller Technique,” “Independent Reading,” “Directed Reading Thinking Activity,” and “Say Something” were the leading strategies applied by teachers in the implementation of the program. The majority of the pupils still belonged to the "Frustration" level. However, there was a significant improvement in pupils’ reading performance for three school years. Teachers encountered "Serious" problems in the implementation of the program, while the suggested solutions were considered as "Very Effective." Furthermore, there was no significant difference between the assessments of the two groups of respondents on the effectiveness of the CNR program

Estar "Indo Bem" é Algo Bom? Como webanalytics e mídias sociais trazem í tona uma nova norma jornalística

Este estudo examina como jornalistas on-line definem uma frase comumente ouvida no ambiente de redação online: o que significa se uma história está "indo bem"? Por meio de análise qualitativa das respostas obtidas por pesquisa com 206 editores on-line, tal estudo encontrou cinco categorias gerais de definição: a) receber muitos leitores; b) obter altas métricas de audiência; c) ser compartilhada nas mídias sociais; d) ser comentada pelos leitores; e) contribuir aos papéis sociais do jornalismo. A plausibilidade dessa prática emergente como uma nova norma jornalística é, então, discutida

What Is (Fake) News? Analyzing News Values (and More) in Fake Stories

‘Fake news’ has been a topic of controversy during and following the 2016 U.S. presidential election. Much of the scholarship on it to date has focused on the ‘fakeness’ of fake news, illuminating the kinds of deception involved and the motivations of those who deceive. This study looks at the ‘newsness’ of fake news by examining the extent to which it imitates the characteristics and conventions of traditional journalism. Through a content analysis of 886 fake news articles, we find that in terms of news values, topic, and formats, articles published by fake news sites look very much like traditional—and real—news. Most of their articles included the news values of timeliness, negativity, and prominence; were about government and politics; and were written in an inverted pyramid format. However, one point of departure is in terms of objectivity, operationalized as the absence of the author’s personal opinion. The analysis found that the majority of articles analyzed included the opinion of their author or authors

Editorial: Diversity in Digital Journalism

This editorial intends to shine a spotlight on diversity in Digital Journalism scholarship. In celebration of International Women’s Day this year, the Digital Journalism editorial team led an initiative involving some of the world’s leading journals in journalism, communication, media studies, and media management, to provide free access to a series of important articles by female authors. In continuation of what was started on International Women’s Day, this editorial and this virtual special issue presents a collection of research providing some of the best examples of groundbreaking, leading research in Digital Journalism Studies by women. These articles have been selected because they represent different cultural perspectives and/or offer excellent theoretical or empirical scholarship for us to utilize and extend as a global network of scholars. They show why we need to embrace, not ignore, our full community of researchers and their work, as they make it clear that doing so will only enrich the quality of research and encourage a more global, inclusive conversation about digital journalism in these times.</p