Author Correction: Regulatory feedback from nascent RNA to chromatin and transcription.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Regulatory feedback from nascent RNA to chromatin and transcription.

Transcription and chromatin function are regulated by proteins that bind to DNA, nucleosomes or RNA polymerase II, with specific non-coding RNAs (ncRNAs) functioning to modulate their recruitment or activity. Unlike ncRNAs, nascent pre-mRNA was considered to be primarily a passive player in these processes. In this Opinion article, we describe recently identified interactions between nascent pre-mRNAs and regulatory proteins, highlight commonalities between the functions of nascent pre-mRNA and nascent ncRNA, and propose that both types of RNA have an active role in transcription and chromatin regulation.

CircAFF1 Is a Circular RNA with a Role in Alveolar Rhabdomyosarcoma Cell Migration.

Circular RNAs (circRNAs), covalently closed RNAs that originate from back-splicing events, participate in the control of several processes, including those that occur in the development of pathological conditions such as cancer. Hereby, we describe circAFF1, a circular RNA overexpressed in alveolar rhabdomyosarcoma. Using RH4 and RH30 cell lines, a classical cell line models for alveolar rhabdomyosarcoma, we demonstrated that circAFF1 is a cytoplasmatic circRNA and its depletion impacts cell homeostasis favouring cell migration through the downregulation of genes involved in cell adhesion pathways. The presented data underline the importance of this circular RNA as a new partial suppressor of the alveolar rhabdomyosarcoma tumour progression and as a putative future therapeutic target.

The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs.

N6-Methyladenosine (m6A) is well-known for controlling different processes of linear RNA metabolism. Conversely, its role in the biogenesis and function of circular RNAs (circRNAs) is still poorly understood. Here, we characterize circRNA expression in the pathological context of rhabdomyosarcoma (RMS), observing a global increase when compared to wild-type myoblasts. For a set of circRNAs, such an increase is due to the raised expression of the m6A machinery, which we also find to control the proliferation activity of RMS cells. Furthermore, we identify the RNA helicase DDX5 as a mediator of the back-splicing reaction and as a co-factor of the m6A regulatory network. DDX5 and the m6A reader YTHDC1 are shown to interact and to promote the production of a common subset of circRNAs in RMS. In line with the observation that YTHDC1/DDX5 depletion reduces RMS proliferation, our results provide proteins and RNA candidates for the study of rhabdomyosarcoma tumorigenicity.

CircVAMP3: A circRNA with a Role in Alveolar Rhabdomyosarcoma Cell Cycle Progression.

Circular RNAs (circRNAs), a class of covalently closed RNAs formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in RH4, a representative cell line of alveolar rhabdomyosarcoma. We demonstrated that circVAMP3 has a differential m6A pattern opposed to its linear counterpart, suggesting that the two isoforms can be differently regulated by such RNA modification. Moreover, we show how circVAMP3 depletion in alveolar rhabdomyosarcoma cells can impair cell cycle progression, through the alteration of the AKT-related pathways, pointing to this non-coding RNA as a novel regulator of the alveolar rhabdomyosarcoma progression and as a putative future therapeutic target.

[Exposure to environmental tobacco smoke and salivary cotinine concentration in a sample of students from Barcelona, Spain]. / Exposición al humo de tabaco y concentración de cotinina en la saliva en una muestra de escolares de Barcelona.

BACKGROUND AND OBJECTIVE: The objective of this study was to assess the exposure to environmental tobacco smoke (ETS) by means of the concentration of salivary cotinine in a sample of adolescent students, and its relationship with active and passive tobacco consumption. METHODS: A cross-sectional survey was conducted in 92 secondary education and high school pupils (16-20 years). Salivary samples were collected and salivary cotinine was measured by gas chromatography/mass spectrometry. Salivary cotinine medians and interquartile ranges were calculated. Significant statistical differences were detected with the non parametric test for medians. RESULTS: The median of salivary cotinine concentration in current smokers was 91.5 ng/ml (RI: 62.4-125); in former smokers 7.9 ng/ml (RI: 5.1-15.5) and in never smokers 1.9 ng/ml (RI: 0-3.6). In smokers of more than 10 cigarettes per day, the result was 98.3 ng/ml (RI:63.4-142.9). Among non-smokers (never-smoker and ex-smokers), the median of salivary cotinine in non-smokers living with smokers was 3.3 ng/ml (RI: 0-8.6) versus 2.9 ng/ml (RI: 1.1-6.9) in those living with non-smokers. CONCLUSIONS: The salivary cotinine concentration increases with the intensity of tobacco consumption and the perception of passive exposure to tobacco smoke.

Evaluation of the effectiveness of a school-based cannabis prevention program.

BACKGROUND: The effectiveness of a cannabis prevention program in high school students was assessed. METHODS: A quasi-experimental study was designed to evaluate the effectiveness of an intervention implemented in an intervention group (IG) with 39 schools compared with a control group (CG) of 47 schools not exposed to the intervention. Of 224 secondary schools in Barcelona, 86 were assessed in the 2005-2006 school year through a personal questionnaire administered at baseline and 15 months after the intervention. Participants consisted of 4848 ninth graders (14-15 year-olds), 2803 assigned to the IG and 2043 to the CG, according to the type and size of the school and the socioeconomic status of the school's neighborhood. The intervention consisted of a school-based cannabis prevention program (xkpts.com), with four sessions and 16 activities, implemented over 6-10h, with materials for parents and web-based student involvement. Last-month cannabis use was assessed at baseline and at 15 months' follow-up. Process evaluation indicators were assessed. RESULTS: At 15 months follow-up, 8.2% of boys and 8.3% of girls in the IG became last-month cannabis users versus 11.8% of boys and 11.6% of girls in the CG. These differences were statistically significant (p=0.003), representing a 29% reduction in last-month cannabis users in the IG compared with the CG. The incidence of last-month cannabis use was lowest in classrooms that adhered to the program protocol. CONCLUSIONS: The xkpts.com program was effective in preventing progression to last-month cannabis use. Effectiveness was higher in classrooms that adhered closely to the protocol.