No abstract

Summary How genes are regulated to produce the correct assortment of proteins for every cell type is a fundamental question in biology. For many genes, regulation begins at the DNA level using promoter sequences to control transcription. Regulation can also occur after transcription using sequences in the 3’ untranslated region (UTR) of the mRNA to affect mRNA stability and/or translation. Using a transgenic assay, we have compared the contribution of promoters and 3’UTRs to gene regulation in the C. elegans germline. We find that for most genes tested, 3’ UTRs were sufficient for regulation. With the exception of promoters activated during spermatogenesis, promoters were permissive for expression in all germ cell types (from undifferentiated progenitors to mature oocytes and sperm) and showed no cell-type specificity. In progenitors, 3’ UTRs inhibit the production of meiotic and oocyte proteins by post-transcriptional mechanisms involving two classes of RNA-binding proteins (PUF and KH domain proteins). Our findings indicate that many genes rely primarily on 3’UTRs, not promoters, for regulation during germline development.

Elastography is a method that can ultimately generate several new kinds of images, called elastograms. As such, all the properties of elastograms are different from the familiar properties of sonograms. While sonograms convey information related to the local acoustic backscatter energy from tissue components, elastograms relate to its local strains, Young's moduli or Poisson's ratios. In general, these elasticity parameters are not directly correlated with sonographic parameters, i.e. elastography conveys new information about internal tissue structure and behavior under load that is not otherwise obtainable. In this paper we summarize our work in the field of elastography over the past decade. We present some relevant background material from the field of biomechanics. We then discuss the basic principles and limitations that are involved in the production of elastograms of biological tissues. Results from biological tissues in vitro and in vivo are shown to demonstrate this point. We conclude with some observations regarding the potential of elastography for medical diagnosis.

Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3′ untranslated region (3′ UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3′UTR elements in both Erk2 and p38α mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38α 3′ UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.