Chicken, rat and human U1A RNAs in solution, were examined for secondary structure, using several methods including hydrolysis by various nucleases, hybridization to DNA oligomers and analysis of fragment interactions. The experimental results showed that the three U1A RNAs have the same structure, stable over a wide range of pH and ionic conditions. They allowed the selection of one out of several possible models constructed from the data of primary structure. This model is characterized by 4 hairpins and two single-stranded regions, the two hairpins from the 3' part of the molecule bearing very stable stems. In addition, the experimental results showed that in contrast to the 5' half of the molecule, the 3' half has a compact conformation probably stabilized by tertiary interactions. The 5' end of U1A RNA is accessible and free of base-pairing so that it might base-pair with regions of other RNA molecules, for instance, with the extremities of introns as has been recently proposed in a model of splicing.

Corneodesmosomes, the modified desmosomes of the uppermost layers of the epidermis, play an important role in corneocyte cohesion. Corneodesmosin is a secreted glycoprotein located in the corneodesmosomal core and covalently linked to the cornified envelope of corneocytes. Its glycine-and serine-rich NH 2 -terminal domain may fold to give structural motifs similar to the glycine loops described in epidermal cytokeratins and loricrin and proposed to display adhesive properties. A chimeric protein comprising human corneodesmosin linked to the transmembrane and cytoplasmic domains of mouse E-cadherin was expressed in mouse fibroblasts to test the ability of corneodesmosin to promote cell-cell adhesion. Classic aggregation assays indicated that corneodesmosin mediates homophilic cell aggregation. Moreover, Ca 2؉ depletion showed a moderate effect on aggregation. To assess the involvement of the glycine loop domain in adhesion, full-length corneodesmosin, corneodesmosin lacking this domain, or this domain alone were expressed as glutathione S-transferase fusion proteins and tested for protein-protein interactions by overlay binding assays. The results confirmed that corneodesmosin presents homophilic interactions and indicated that its NH 2 -terminal glycine loop domain is sufficient but not strictly necessary to promote binding. Altogether, these results provide the first experimental evidence for the adhesive properties of corneodesmosin and for the involvement of its glycine loop domain in adhesion.In the course of their differentiation program, epidermal keratinocytes undergo cornification, a complex set of biochemical events associated with major morphological modifications, resulting in their transformation into corneocytes. Corneocytes, devoid of tripartite plasma membrane, are limited by a highly cross-linked insoluble protein shell, the cornified envelope (1-3). Cornification induces structural modifications of the keratinocyte desmosomes, including the disappearance of the cytoplasmic plaque that is incorporated in the cornified envelope, and the densification of the desmoglea. However, the mechanisms underlying their transformation into corneodesmosomes are still poorly understood. Corneodesmosomes mediate the strong intercellular cohesion in the cornified layers that is crucial for the physical and chemical barrier function of the epidermis. Ultimately, they are degraded at the time of desquamation (4).Human corneodesmosin (Cdsn), 1 a 52-to 56-kDa basic glycoprotein specific to the cornified epithelia and the inner root sheath of the hair follicles, is firstly detected in the secretory vesicles (i.e. keratinosomes) of the keratinocytes of the uppermost spinous layer and granular layer. It is also present in the extracellular part of the granular keratinocyte desmosomes and remains in these structures after their transformation into corneodesmosomes. In the cornified layers, Cdsn is covalently linked to the cornified envelope (5-7).Cdsn has a very high serine and glycine content (27.5 and 16%, respectively...