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Full-Text Articles in Life Sciences

The Trnaval Half: A Strong Endogenous Toll-Like Receptor 7 Ligand With A 5′-Terminal Universal Sequence Signature, Kamlesh Ganesh Pawar, Takuya Kawamura, Yohei Kirino May 2024

The Trnaval Half: A Strong Endogenous Toll-Like Receptor 7 Ligand With A 5′-Terminal Universal Sequence Signature, Kamlesh Ganesh Pawar, Takuya Kawamura, Yohei Kirino

Computational Medicine Center Faculty Papers

Toll-like receptors (TLRs) are crucial components of the innate immune system. Endosomal TLR7 recognizes single-stranded RNAs, yet its endogenous ssRNA ligands are not fully understood. We previously showed that extracellular (ex-) 5'-half molecules of tRNAHisGUG (the 5'-tRNAHisGUG half) in extracellular vesicles (EVs) of human macrophages activate TLR7 when delivered into endosomes of recipient macrophages. Here, we fully explored immunostimulatory ex-5'-tRNA half molecules and identified the 5'-tRNAValCAC/AAC half, the most abundant tRNA-derived RNA in macrophage EVs, as another 5'-tRNA half molecule with strong TLR7 activation capacity. Levels of the ex-5'-tRNAValCAC/AAC half were highly up-regulated in macrophage EVs …


The Typical Trna Co-Expresses Multiple 5' Trna Halves Whose Sequences And Abundances Depend On Isodecoder And Isoacceptor And Change With Tissue Type, Cell Type, And Disease, Robert Akins, Kayleigh Ostberg, Tess Cherlin, Nikolas Tsiouplis, Phillipe Loher, Isidore Rigoutsos Nov 2023

The Typical Trna Co-Expresses Multiple 5' Trna Halves Whose Sequences And Abundances Depend On Isodecoder And Isoacceptor And Change With Tissue Type, Cell Type, And Disease, Robert Akins, Kayleigh Ostberg, Tess Cherlin, Nikolas Tsiouplis, Phillipe Loher, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

Transfer RNA-derived fragments (tRFs) are noncoding RNAs that arise from either mature transfer RNAs (tRNAs) or their precursors. One important category of tRFs comprises the tRNA halves, which are generated through cleavage at the anticodon. A given tRNA typically gives rise to several co-expressed 5'-tRNA halves (5'-tRHs) that differ in the location of their 3' ends. These 5'-tRHs, even though distinct, have traditionally been treated as indistinguishable from one another due to their near-identical sequences and lengths. We focused on co-expressed 5'-tRHs that arise from the same tRNA and systematically examined their exact sequences and abundances across 10 different human …


The Role Of Non-Coding Rnas In Myelodysplastic Neoplasms, Vasileios Georgoulis, Epameinondas Koumpis, Eleftheria Hatzimichael Sep 2023

The Role Of Non-Coding Rnas In Myelodysplastic Neoplasms, Vasileios Georgoulis, Epameinondas Koumpis, Eleftheria Hatzimichael

Computational Medicine Center Faculty Papers

Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia, and increased risk of evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs, serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis. This review presents a comprehensive summary of the biology and role of non-coding RNAs, including the less studied circRNA, siRNA, piRNA, and snoRNA as potential prognostic and/or predictive biomarkers or therapeutic targets in MDS.


Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko Sep 2023

Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko

Computational Medicine Center Faculty Papers

The elimination of lens organelles during development, required for mature lens function, is an autophagy-dependent mechanism induced through suppression of PI3K signaling. Here, we present a protocol for investigating the signaling pathways responsible for induction of the formation of this lens organelle free zone. We describe steps for preparation of lens organ culture and use of signaling pathway inhibitors. We then detail procedures for analyzing their impact using both confocal microscopy imaging of immunolabeled lens cryosections and immunoblot approaches. For complete details on the use and execution of this protocol, please refer to Gheyas et al. (2022).


Immune Cells Localize To Sites Of Corneal Erosions In C57bl/6 Mice., Phuong M. Le, Sonali Pal-Ghosh, A. Menko, Mary Ann Stepp Jun 2023

Immune Cells Localize To Sites Of Corneal Erosions In C57bl/6 Mice., Phuong M. Le, Sonali Pal-Ghosh, A. Menko, Mary Ann Stepp

Computational Medicine Center Faculty Papers

Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent erosions in animal models allow us to gain insight into how erosions form and are resolved. While slowing corneal epithelial cell migration and reducing their proliferation following treatment with mitomycin C reduce erosion formation in mice after sterile debridement injury, additional factors have been identified related to cytokine expression and immune cell activation. The relationship between recruitment of immune cells to the region of the cornea where erosions form and their potential roles in erosion formation and/or erosion repair remains unexplored in the …


Challenges Inherent To The Sequencing And Quantification Of Short Non-Coding Rnas And How To Address Them, Justin Gumas, Yohei Kirino Jun 2022

Challenges Inherent To The Sequencing And Quantification Of Short Non-Coding Rnas And How To Address Them, Justin Gumas, Yohei Kirino

Computational Medicine Center Faculty Papers

No abstract provided.


Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino Jul 2021

Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino

Computational Medicine Center Faculty Papers

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated …


Stategra: Multi-Omics Data Integration - A Conceptual Scheme With A Bioinformatics Pipeline, Nuria Planell, Vincenzo Lagani, Patricia Sebastian-Leon, Frans Van Der Kloet, Ewoud Ewing, Nestoras Karathanasis, Arantxa Urdangarin, Imanol Arozarena, Maja Jagodic, Ioannis Tsamardinos, Sonia Tarazona, Ana Conesa, Jesper Tegner, David Gomez-Cabrero Mar 2021

Stategra: Multi-Omics Data Integration - A Conceptual Scheme With A Bioinformatics Pipeline, Nuria Planell, Vincenzo Lagani, Patricia Sebastian-Leon, Frans Van Der Kloet, Ewoud Ewing, Nestoras Karathanasis, Arantxa Urdangarin, Imanol Arozarena, Maja Jagodic, Ioannis Tsamardinos, Sonia Tarazona, Ana Conesa, Jesper Tegner, David Gomez-Cabrero

Computational Medicine Center Faculty Papers

Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. Therefore, it is an unmet need to conceptualize how to integrate such data and implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining …


Genome-Wide Identification Of Short 2',3'-Cyclic Phosphate-Containing Rnas And Their Regulation In Aging., Megumi Shigematsu, Keisuke Morichika, Takuya Kawamura, Shozo Honda, Yohei Kirino Nov 2019

Genome-Wide Identification Of Short 2',3'-Cyclic Phosphate-Containing Rnas And Their Regulation In Aging., Megumi Shigematsu, Keisuke Morichika, Takuya Kawamura, Shozo Honda, Yohei Kirino

Computational Medicine Center Faculty Papers

RNA molecules generated by ribonuclease cleavage sometimes harbor a 2',3'-cyclic phosphate (cP) at their 3'-ends. Those cP-containing RNAs (cP-RNAs) form a hidden layer of transcriptome because standard RNA-seq cannot capture them as a result of cP's prevention of an adapter ligation reaction. Here we provide genome-wide analyses of short cP-RNA transcriptome across multiple mouse tissues. Using cP-RNA-seq that can exclusively sequence cP-RNAs, we identified numerous novel cP-RNA species which are mainly derived from cytoplasmic tRNAs, mRNAs, and rRNAs. Determination of the processing sites of substrate RNAs for cP-RNA generation revealed highly-specific RNA cleavage events between cytidine and adenosine in cP-RNA …