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Specialized ribosomes: a new frontier in gene expression and organismal development (213.3)
Author(s) -
Barna Maria
Publication year - 2014
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.28.1_supplement.213.3
Subject(s) - biology , ribosome , translation (biology) , computational biology , gene , cell fate determination , gene expression , regulation of gene expression , multicellular organism , microbiology and biotechnology , genetics , rna , messenger rna , transcription factor
The regulatory logic for how the one‐dimensional genetic code is translated into three‐dimensional morphology in a multicellular organism poses one of the greatest challenges to modern biology. Notably, the prevailing dogma has been that the ribosome is an integral but passive participant in directing how the genome is functionally expressed. Our findings unexpectedly reveal that fundamental aspects of gene regulation and mammalian development are instead controlled by “specialized ribosomes,” harboring a unique composition or activity, which direct where and when specific proteins are made. For example, we have identified that RPL38, one of the approximately 80 core ribosomal proteins (RPs), acts to establish the mammalian body plan by selectively regulating the translation of Homeobox mRNAs, key master regulators of animal development. These findings suggest newfound specificity to how the genomic template is decoded into proteins to instruct key cell fate decisions. Collectively, our ongoing work seeks to define the regulatory basis by which “specialized ribosomes” control gene expression. I will present our recent findings that identify novel cis‐acting RNA elements within mammalian 5’ UTRs, which act as regulatory filters that interface with specialized ribosomes to regulate spatial‐temporal gene expression in vivo. We have also carried out state‐of‐the‐art mass spectrometry to delineate for the first time ribosome heterogeneity during cellular differentiation and to define the repertoire of transcripts that rely on specialized ribosome components for cell fate specification and differentiation. Together, these studies reveal that specialized translational machinery in conjunction with unique cis‐acting RNA elements within the 5’ UTRs of mammalian mRNAs provide a new layer of regulatory control to gene expression that guides evolution and organismal development.