The region 3 ' to C alpha 1 gene of human IG heavy chain displays a polymorphic duplicated sequence and encodes an RNA associated with polysomes

A highly spread polymorphism flanking the 3 C alpha 1 human IG heavy chain gene was identified. This polymorphism allowed the detection of an internal duplication within the 3' flanking region of both C alpha 1 and C alpha 2. This region has a regulatory function with four enhancer structures also present at the 3' end of the human C alpha 2 as well as in that of mouse and rat single C alpha genes. The 5682-bp sequence of clone lambda p18 described here starts 3' of C alpha 1 and presents three open reading frames; one of them contains part of the tandem repeats with the 20-bp consensus described previously that is expressed in a poly(A)(+) RNA and found in three dbEST clones of the human tonsillar cDNA library. Here, we demonstrate that in the CLF1 B lymphoblastoid cell line, this transcript is associated with polysomes. We also discuss the possibility of the presence of a new regulatory gene that does not encode an immunoglobulin and maps in the human IG heavy chain gene cluster. (C) 1998 Elsevier Science B.V. All rights reserved

Flat absorbance background for sucrose gradients

[No abstract available

Growth-dependent and growth-independent translation of messengers for heterogeneous nuclear ribonucleoproteins

The hnRNP A1 transcript has a relatively short 5'-untranslated region (UTR) starting with a pyrimidine tract similar to that of mRNAs encoded by the TOP [terminal oligo(pyrimidine)] genes in vertebrates. Such genes code for ribosomal proteins and for other proteins directly or indirectly involved in the production and function of the translation apparatus. As expected from the role of the pyrimidine tract in the translational regulation of TOP mRNAs, the A1 mRNA is more efficiently loaded onto polysomes in growing than in resting cells. On the other hand, a less stringent regulation with respect to that of other TOP mRNAs is observed, partially due to the presence of multiple transcription start, sites within the pyrimidine tract, where transcripts with shorter TOP sequences are less sensitive to regulation. Thus, from the point of view of structural features and translation behaviour the A1 mRNA can be included in the class of TOP genes, suggesting a possible role of A1 in translation, Interestingly, a TOP-like behaviour was observed for hnRNP I mRNA but not for hnRNP C1/C2 and A2/B1 mRNAs, indicating the existence of two classes of hnRNPs with different translational regulation

The Impact of Simvastatin on Pulmonary Effectors of Pseudomonas aeruginosa Infection

The statin family of cholesterol-lowering drugs is known to have pleiotropic properties which include anti-inflammatory and immunomodulatory effects. Statins exert their pleiotropic effects by altering expression of human immune regulators including pro-inflammatory cytokines. Previously we found that statins modulate virulence phenotypes of the human pathogen Pseudomonas aeruginosa, and sought to investigate if simvastatin could alter the host response to this organism in lung epithelial cells. Simvastatin increased the expression of the P. aeruginosa target genes KLF2, KLF6, IL-8 and CCL20.Furthermore, both simvastatin and P. aeruginosa induced alternative splicing of KLF6. The novel effect of simvastatin on wtKLF6 expression was found to be responsible for induction of the KLF6 regulated genes CCL20 and iNOS. Simvastatin also increased the adhesion of P. aeruginosa to host cells, without altering invasion or cytotoxicity. This study demonstrated that simvastatin had several novel effects on the pulmonary cellular immune response