Human ribosomal protein S13 regulates expression of its own gene at the splicing step by a feedback mechanism

Abstract

The expression of ribosomal protein (rp) genes is regulated at multiple levels. In yeast, two genes are autoregulated by feedback effects of the protein on pre-mRNA splicing. Here, we have investigated whether similar mechanisms occur in eukaryotes with more complicated and highly regulated splicing patterns. Comparisons of the sequences of ribosomal protein S13 gene (RPS13) among mammals and birds revealed that intron 1 is more conserved than the other introns. Transfection of HEK 293 cells with a minigene-expressing ribosomal protein S13 showed that the presence of intron 1 reduced expression by a factor of four. Ribosomal protein S13 was found to inhibit excision of intron 1 from rpS13 pre-mRNA fragment in vitro. This protein was shown to be able to specifically bind the fragment and to confer protection against ribonuclease cleavage at sequences near the 5′ and 3′ splice sites. The results suggest that overproduction of rpS13 in mammalian cells interferes with splicing of its own pre-mRNA by a feedback mechanism.

RpS3 translation is repressed by interaction with its own mRNA

“…This phenomenon has been observed in mammalian ribosomal proteins as well [Neumann et al, 1995;Tasheva and Roufa, 1995]. Upon overexpression, rpS13 [Malygin et al, 2007] and rpS26 [Ivanov et al, 2005] bind the introns of their own pre-mRNA to suppress splicing.…”

Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program

“…For instance, rpS13 downregulates its own expression by binding the pre-mRNA and inhibiting splicing. 49 RpL11 interacts with and inhibits the transcription factor Myc that drives transcription of 5S rRNA and transfer RNA genes as well as of RP genes. 50 In yeast, the binding of RPs to the gene promoters is enriched at the transfer RNA genes.…”

Cellular Differences in Protein Synthesis Regulate Tissue Homeostasis

“…Ribosome proteins can also exhibit important functions outside the ribosome, complicating the interpretation of at least some mutant phenotypes (Xue and Barna, 2012). For example, Rps13 regulates the splicing of its own message (Malygin et al, 2007) and ribosomes can bind mTORC2 and promote its signaling in a translation independent manner (Zinzalla et al, 2011). It remains unclear whether extra-ribosomal functions are unusual properties pertaining to a minority of ribosome components or whether many ribosome components have unrecognized extra-ribosomal functions, including cell type-specific functions.…”