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The JAK‐STAT pathway is regulated by miRNA mediated Ribosomal Frameshifting
Author(s) -
Dinman Jonathan D.,
Khan Yousuf A.,
Advani Vivek M.,
Flickenger Zachary R
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1060.1
Subject(s) - translational frameshift , biology , microbiology and biotechnology , translational regulation , ribosome , stat protein , signal transduction , translation (biology) , messenger rna , gene , genetics , rna , stat3
Programmed −1 ribosomal frameshifting (‐1 PRF) is a translational recoding mechanism whereby a translating ribosome is induced to slip one nucleotide in the 5′ direction by a complex mRNA cis ‐acting element (1). In the context of cellular mRNAs, such events overwhelmingly direct ribosome to premature termination codons (PTC), rendering these mRNAs substrates for the nonsense mediated mRNA decay (NMD) pathway (2). Approximately 10% of all human genes have at least one predicted significant −1 PRF motif, suggesting that −1 PRF is extensively used to regulate gene expression in human cells (3). Here we have characterized the −1 PRF signals in the mRNAs encoding human Janus Kinase 2 (JAK2) and Signal Transducer and Activator 1 (STAT1), both of which are involved in JAK/STAT intracellular signaling. Efficient −1 PRF by these sequence elements was confirmed both genetically and biochemically. Preliminary data suggests that JAK2‐mediated −1 PRF is inhibited by two miRNAs in a sequence specific manner. Furthermore, Jak2‐mediated −1 PRF appears to be involved in a regulatory feedback loop with cytokine signaling. Studies are underway to characterize the role of −1 PRF and the miRNAs in regulating the JAK‐STAT pathway. This study will serve to understand the role of translational recoding in immune signaling. Support or Funding Information NIH R01HL119439, NIH R01GM117177