SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies

Author:

Toki Naoko12ORCID,Takahashi Hazuki12ORCID,Sharma Harshita1,Valentine Matthew N Z1ORCID,Rahman Ferdous-Ur M1ORCID,Zucchelli Silvia3,Gustincich Stefano4,Carninci Piero12ORCID

Affiliation:

1. Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045 Japan

2. Functional Genomics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan

3. Department of Health Sciences, Center for Autoimmune and Allergic Diseases (CAAD) and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, Italy

4. Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy

Abstract

Abstract SINEUPs are long non-coding RNAs (lncRNAs) that contain a SINE element, and which up-regulate the translation of target mRNA. They have been studied in a wide range of applications, as both biological and therapeutic tools, although the underpinning molecular mechanism is unclear. Here, we focused on the sub-cellular distribution of target mRNAs and SINEUP RNAs, performing co-transfection of expression vectors for these transcripts into human embryonic kidney cells (HEK293T/17), to investigate the network of translational regulation. The results showed that co-localization of target mRNAs and SINEUP RNAs in the cytoplasm was a key phenomenon. We identified PTBP1 and HNRNPK as essential RNA binding proteins. These proteins contributed to SINEUP RNA sub-cellular distribution and to assembly of translational initiation complexes, leading to enhanced target mRNA translation. These findings will promote a better understanding of the mechanisms employed by regulatory RNAs implicated in efficient protein translation.

Funder

Ministry of Education, Culture, Sports, Science and Technology

Japan Agency for Medical Research and Development

JSPS KAKENHI

Publisher

Oxford University Press (OUP)

Subject

Genetics

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