Suppression of Epidermal Growth Factor Receptor by Erlotinib Attenuates Carvacrol-induced Skin Inflammation.

Epidermal growth factor receptors (EGFRs) regulate the growth and repair process of epithelia, as well as carcinogenesis. Activation of TRPV3 by carvacrol stimulates skin inflammation and epidermal hyperplasia; the latter can be suppressed by EGFR inhibition. However, whether EGFR signalling is responsible for skin inflammation remains elusive.

Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection.

Circular RNAs (circRNAs) generated via back-splicing are enhanced by flanking complementary sequences. Expression levels of circRNAs vary under different conditions, suggesting participation of protein factors in their biogenesis. Using genome-wide siRNA screening that targets all human unique genes and an efficient circRNA expression reporter, we identify double-stranded RNA-binding domain containing immune factors NF90/NF110 as key regulators in circRNA biogenesis.

Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding Proteins.

We identify a type of polycistronic transcript-derived long noncoding RNAs (lncRNAs) that are 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated (SPAs). SPA processing is associated with nascent mRNA 3' processing and kinetic competition between XRN2 trimming and Pol II elongation. Following cleavage/polyadenylation of its upstream gene, the downstream uncapped pre-SPA is trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled snoRNP.

Gene expression profiling of non-polyadenylated RNA-seq across species.

Transcriptomes are dynamic and unique, with each cell type/tissue, developmental stage and species expressing a different repertoire of RNA transcripts. Most mRNAs and well-characterized long noncoding RNAs are shaped with a 5' cap and 3' poly(A) tail, thus conventional transcriptome analyses typically start with the enrichment of poly(A)+ RNAs by oligo(dT) selection, followed by deep sequencing approaches. However, accumulated lines of evidence suggest that many RNA transcripts are processed by alternative mechanisms without 3' poly(A) tails and, therefore, fail to be enriched by oligo(dT) purification and are absent following deep sequencing analyses.

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner.

Adenosine deaminases acting on RNA (ADARs) are involved in adenosine-to-inosine RNA editing and are implicated in development and diseases. Here we observed that ADAR1 deficiency in human embryonic stem cells (hESCs) significantly affected hESC differentiation and neural induction with widespread changes in mRNA and miRNA expression, including upregulation of self-renewal-related miRNAs, such as miR302s. Global editing analyses revealed that ADAR1 editing activity contributes little to the altered miRNA/mRNA expression in ADAR1-deficient hESCs upon neural induction.

SnoVectors for nuclear expression of RNA.

Many long noncoding RNAs (lncRNAs) are constrained to the nucleus to exert their functions. However, commonly used vectors that were designed to express mRNAs have not been optimized for the study of nuclear RNAs. We reported recently that sno-lncRNAs are not capped or polyadenylated but rather are terminated on each end by snoRNAs and their associated proteins.

Fractionation of non-polyadenylated and ribosomal-free RNAs from mammalian cells.

Most of mRNAs and well-characterized long noncoding RNAs are shaped with 5' cap and 3' poly(A) tail. Thereby, conventional transcriptome analysis typically involved the enrichment of poly(A)+ RNAs by oligo(dT) selection. However, accumulated lines of evidence suggest that there are many RNA transcripts processed in alternative ways, which largely failed to be detected by oligo(dT) purification.

Species-specific alternative splicing leads to unique expression of sno-lncRNAs.

Background: Intron-derived long noncoding RNAs with snoRNA ends (sno-lncRNAs) are highly expressed from the imprinted Prader-Willi syndrome (PWS) region on human chromosome 15. However, sno-lncRNAs from other regions of the human genome or from other genomes have not yet been documented.

Results: By exploring non-polyadenylated transcriptomes from human, rhesus and mouse, we have systematically annotated sno-lncRNAs expressed in all three species.

Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus.

The human 8q24 gene desert contains multiple enhancers that form tissue-specific long-range chromatin loops with the MYC oncogene, but how chromatin looping at the MYC locus is regulated remains poorly understood. Here we demonstrate that a long noncoding RNA (lncRNA), CCAT1-L, is transcribed specifically in human colorectal cancers from a locus 515 kb upstream of MYC. This lncRNA plays a role in MYC transcriptional regulation and promotes long-range chromatin looping.

Circular intronic long noncoding RNAs.

We describe the identification and characterization of circular intronic long noncoding RNAs in human cells, which accumulate owing to a failure in debranching. The formation of such circular intronic RNAs (ciRNAs) can be recapitulated using expression vectors, and their processing depends on a consensus motif containing a 7 nt GU-rich element near the 5' splice site and an 11 nt C-rich element close to the branchpoint site. In addition, we show that ciRNAs are abundant in the nucleus and have little enrichment for microRNA target sites.

Long noncoding RNAs with snoRNA ends.

We describe the discovery of sno-lncRNAs, a class of nuclear-enriched intron-derived long noncoding RNAs (lncRNAs) that are processed on both ends by the snoRNA machinery. During exonucleolytic trimming, the sequences between the snoRNAs are not degraded, leading to the accumulation of lncRNAs flanked by snoRNA sequences but lacking 5' caps and 3' poly(A) tails. Such RNAs are widely expressed in cells and tissues and can be produced by either box C/D or box H/ACA snoRNAs.