Coordinated Control of mRNA and rRNA Processing Controls Embryonic Stem Cell Pluripotency and Differentiation
CELL STEM CELL
Authors: Corsini, Nina S.; Peer, Angela M.; Moeseneder, Paul; Roiuk, Mykola; Burkard, Thomas R.; Theussl, Hans-Christian; Moll, Isabella; Knoblich, Juergen A.
Abstract
Stem cell-specific transcriptional networks are well known to control pluripotency, but constitutive cellular processes such as mRNA splicing and protein synthesis can add complex layers of regulation with poorly understood effects on cell-fate decisions. Here, we show that the RNA binding protein HTATSF1 controls embryonic stem cell differentiation by regulating multiple aspects of RNA processing during ribosome biogenesis. HTATSF1, in a complex with splicing factor SF3B1, controls intron removal from ribosomal protein transcripts and regulates ribosomal RNA transcription and processing, thereby controlling 60S ribosomal abundance and protein synthesis. HTATSF1-dependent protein synthesis is essential for naive pre-implantation epiblast to transition into post-implantation epiblast, a stage with transiently low protein synthesis, and further differentiation toward neuroectoderm. Together, these results identify coordinated regulation of ribosomal RNA and protein synthesis by HTATSF1 and show that this essential mechanism controls protein synthesis during early mammalian embryogenesis.
Comparative and evolutionary analysis of the rhesus macaque extended MHC class II region
IMMUNOGENETICS
Authors: Sudbrak, R; Reinhardt, R; Hennig, S; Lehrach, H; Gunther, E; Walter, L
Abstract
The sequence-based map of a part of the thesus macaque major histocompatibility complex (MHC) extended class 11 region is presented. The sequenced region encompasses 67,401 bp and contains the SACM2L, RING1, FABGL and KE4 genes, as well as the HTATSF1-like and ZNF-like pseudogenes. Similar to human, but different from rat and mouse, no class I genes are found in the SACM2L-RING1 interval. The rhesus macaque extended MHC class 11 region shows a high degree of conservation of exonic as well as intronic and intergenic sequences compared with the respective human region. It is concluded that this particular genomic organization of the extended class 11 region - i.e., the absence of class I genes and the presence of the HTATSF1-like and ZNF-like pseudogenes - can be traced back to a common ancestor of humans and rhesus macaques about 23 million years ago.