Most ribosomal proteins (RP) are regarded as essential, static components that only contribute to ribosome biogenesis and protein synthesis. However, emerging evidence suggests that RNA-binding RP are dynamic and can influence cellular processes by performing “extraribosomal”, regulatory functions involving binding to select, critical target mRNAs. We report here that the RP, Rpl22, and its highly homologous paralog, Rpl22-Like1 (Rpl22l1 or Like1), play critical, extraribosomal roles in embryogenesis. Indeed, they antagonistically control morphogenesis through developmentally-regulated localization to the nucleus where they modulate splicing of the pre-mRNA encoding smad2, an essential transcriptional effector of Nodal/TGF-ß signaling. During gastrulation, Rpl22 binds to intronic sequences of smad2 pre-mRNA and induces exon 9 skipping in cooperation with hnRNP-A1. This action is opposed by its paralog, Like1, which promotes exon 9 inclusion in the mature transcript. The nuclear roles of these RP in controlling morphogenesis represent a fundamentally different and paradigm-shifting mode of action for RP.

Ribosomal proteins Rpl22 and Rpl22l1 control morphogenesis by regulating pre-mRNA splicing

We evaluated how different microbial species commonly associated with laboratory-reared Drosophila melanogaster impact host biology at the level of gene expression in the dissected adult gut or the entire adult organism. We observed that guts from gnotobiotic animals associated from the embryonic stage with either zero, one or three bacterial species demonstrated indistinguishable transcriptional profiles. Additionally, we found that the gut transcriptional profiles of animals reared in the presence of the yeast Saccharomyces cerevisiae alone or in combination with bacteria could recapitulate those of conventionally-reared animals. In contrast, we found whole body transcriptional profiles of conventionally-reared animals were distinct from all of the gnotobiotic treatments tested. Our data suggest that adult flies are insensitive to the ingestion of different bacterial species but that prior to adulthood, different microbes impact the host in ways that lead to global transcriptional differences observable across the whole adult body.

Drosophila melanogaster strain:CantonS Raw sequence reads

Masseter and Tibialis anterior muscles from adult female control mice to determine expression differences between muscle groups


Expression profiling reveals heightened apoptosis and supports fiber size economy in the murine muscles of mastication.

Transcription profiling of mouse masseter and tibialis anterior muscles to determine expression differences between muscle groups

Gene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection or cell fate choice. The complexity of the molecular steps and machines involved in transcription and translation could introduce sources of randomness at many levels, but a common constraint to most of these processes is its energy dependence. In eukaryotic cells most of this energy is provided by mitochondria. A clonal population of cells may show a large variability in the number and functionality of mitochondria. Cell-to-cell differences in mitochondrial content, probably originated by asymmetric segregation at cell division, contribute to heterogeneity in gene products.

Mitochondrial levels globally modulate gene expression

In the present study, the autologous cell based therapy for the compromised liver disease due to hepatitis B infection has been investigated. To perform this research, the HBsAg positive and nucleic acid test (NAT) positive blood samples along with healthy blood samples were utilized to generate hepatocyte-like cells (NeoHeps) from monocytes. The monocytes were sorted by MACS technology from the PBMCs so that the abundant non-monocyte cells were depleted.The isolated monocytes were cultured in two steps for 21 days. In the first step monocytes were incubated with serum supplemented IMDM medium containing cytokines like IL-3, MCSF and 2-ME for a period of six days for priming to induce plasticity in them. After six day in culture, the primed monocytes were termed as reprogrammed monocytes (RM). The reprogrammed monocytes were then differentiated for 15 days in serum supplemented IMDM medium containing mitogenic reagents like EGF, HGF and FGF-4 to generate NeoHeps.The RNA sequencing (RNASeq) of the Monocytes, RM and NeoHeps generated from both healthy and HBsAg positive blood samples were performed to analyse the kinetics of this differentiation process at the transcript level.

Homo sapiens Raw sequence reads

Temozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance is a major problem limiting its effectiveness. Thus knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion of a regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription of multiple genes. Analysis of a combination of RNA-seq, Capture HiC and patient survival data suggests that CALCOCO1 and ZC3H10 are target genes repressed by the HOTAIR regulatory element and that both function in regulating glioma cell sensitivity to TMZ. Rescue experiments and TAD analysis based on HiC data confirmed this hypothesis. We propose a new regulatory mechanism governing glioma cell TMZ sensitivity.

A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes

Global gene expression analysis of grapevine cv. Pinot Noir berries during development and ripening. Time-course comparison of samples collected at three developmental stages (stages 33, 34 and 36 according to the modified E-L system, ref: Coombe BG, Aust J Grape Wine Res 1995, 1: 104-110) during three seasons (2003, 2005 and 2006).


Genome-wide transcriptional analysis of grapevine berry ripening reveals a set of genes similarly modulated during three seasons and the occurrence of an oxidative burst at vèraison.

Transcription profiling by array of grape cultivar Pinot Noir berry development during three seasons

RNA-Seq study from Caco2 cells following transduction with control shRNA and shRNA against CHD6

Homo sapiens Transcriptome or Gene expression

Alterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute to neoplastic progression.  The importance of the microenvironment in neoplastic progression is underscored by studies demonstrating that fibroblasts isolated from a tumor stimulate the growth of preneoplastic and neoplastic cells in xenograft models.  Similarly, senescent fibroblasts promote preneoplastic cell growth in vitro and in vivo.  Because senescent cells accumulate with age, their presence is hypothesized to facilitate preneoplastic cell growth and tumor formation in older individuals.  To identify senescent stromal factors directly responsible for stimulating preneoplastic cell growth, we carried out whole genome transcriptional profiling and compared senescent fibroblasts to their younger counterparts.  We identified osteopontin (OPN) as one of the most highly elevated transcripts in senescent fibroblasts.   Importantly, reduction of OPN protein levels by RNAi did not impact senescence induction in fibroblasts; however, it dramatically reduced the growth-promoting activities of senescent fibroblasts in vitro and in vivo, demonstrating that OPN is necessary for paracrine stimulation of preneoplastic cell growth.  In addition, we found that recombinant OPN was sufficient to stimulate preneoplastic cell growth.  Finally, we demonstrate that OPN is expressed in senescent stroma within preneoplastic lesions that arise following DMBA/TPA treatment of mice, suggesting that stromal-derived OPN-mediated signaling events impact neoplastic progression.

Senescent stromal-derived osteopontin promotes preneoplastic cell growth.

Senescent Stromal-Derived Osteopontin Promotes Preneoplastic Cell Growth

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