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Shyam Unniraman

Publications and source records attributed to Shyam Unniraman.

8 recordsLinked to original sources
PubMed2006

AID and Igh switch region-Myc chromosomal translocations.

Chromosomal translocations involving Ig heavy chain switch regions and an oncogene, like Myc, represent early initiating events in the development of many B cell malignancies. These translocations are widely believed to result from aberrant class switch recombination (CSR). Recent reports have produced conflicting models for the role of activation-induced cytidine deaminase (AID) in this process. Here, we discuss possible roles of AID, CSR, and somatic hypermutation in generating chromosomal translocations and in tumor progression.

Animals↗
PubMed2005

Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination.

Class switch recombination (CSR) is the process by which B cells alter the effector function properties of their Ig molecules. The decision to switch to a particular Ig isotype is determined primarily by the mode of B cell activation and cytokine exposure. More recent work indicates that the likelihood or probability of switching increases with successive cell divisions and is largely independent of time. We have analyzed different molecular features of CSR using cell division as a reference point in an attempt to gain insight into the mechanism of division-linked switching. Our results indicated that the accessibility of Ig heavy chain constant regions targeted for CSR was established after the cells had undergone a single cell division and did not vary significantly with subsequent cell divisions. In contrast, expression of activation-induced cytidine deaminase (AID) mRNA was found to increase with successive divisions, exhibiting a striking correlation with the frequency of CSR. Levels of AID in a given division remained constant at different time points, strongly suggesting that the regulation of AID expression was division-linked and independent of time. In addition, constitutive AID expression from a transgene accelerated division-linked CSR. Thus, we propose that the division-linked increase in AID expression provides an underlying molecular explanation for division-linked CSR.

Animals↗
PubMed2004

Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc.

Chromosomal translocations involving immunoglobulin heavy chain (Igh) switch regions and an oncogene such as Myc represent initiating events in the development of many B cell malignancies. These translocations are widely thought to result from aberrant class-switch recombination. To test this model, we measured translocations in mice deficient in activation-induced cytidine deaminase (AID) that lack class-switch recombination. We found that AID made no measurable contribution to the generation of initial translocations, indicating that the intrinsic fragility of the switch regions or a pathway unrelated to AID is responsible for these translocations. In contrast, the outgrowth of translocation-positive cells was dependent on AID, raising the possibility that AID is important in tumor progression, perhaps by virtue of its mutagenic properties.

Animals↗
PubMed2002

A hairpin near the 5' end stabilises the DNA gyrase mRNA in Mycobacterium smegmatis.

RNA is amongst the most labile macromolecules present in the cells. The steady-state levels of mRNA are regulated both at the stages of synthesis and degradation. Recent work in Escherichia coli suggests that controlling the rate of degradation is as important as the process of synthesis. The stability of mRNA is probably more important in slow- growing organisms like mycobacteria. Here, we present our analysis of the cis elements that determine the stability of the DNA gyrase message in Mycobacterium smegmatis. The message appears to be stabilised by a structure close to its 5' end. The effect is especially pronounced in a nutrient-depleted state. These results largely parallel the model proposed in E.coli for mRNA degradation/ stability with subtle differences. Furthermore, these results suggest that the slow-growing organisms might use stable mRNAs as a method to reduce the load of transcription on the cell.

5' Untranslated Regions↗
PubMed2002

Conserved economics of transcription termination in eubacteria.

A secondary structure in the nascent RNA followed by a trail of U residues is believed to be necessary and sufficient to terminate transcription. Such structures represent an extremely economical mechanism of transcription termination since they function in the absence of any additional protein factors. We have developed a new algorithm, GeSTer, to identify putative terminators and analysed all available complete bacterial genomes. The algorithm classifies the structures into five classes. We find that potential secondary structure sequences are concentrated downstream of coding regions in most bacterial genomes. Interestingly, many of these structures are not followed by a discernible U-trail. However, irrespective of the nature of the trail sequence, the structures show a similar distribution, indicating that they serve the same purpose. In contrast, such a distribution is absent in archaeal genomes, indicating that they employ a distinct mechanism for transcription termination. The present algorithm represents the fastest and most accurate algorithm for identifying terminators in eubacterial genomes without being restricted by the classical Escherichia coli paradigm.

Algorithms↗
PubMed2002

DNA gyrase genes in Mycobacterium tuberculosis: a single operon driven by multiple promoters.

The two genes encoding DNA gyrase in Mycobacterium tuberculosis are present next to each other in the genome, with gyrB upstream of gyrA. We show that the primary transcript is dicistronic. However, in addition to the principal promoter, there are multiple weaker promoters that appear to fine-tune transcription. With these and other mycobacterial promoters, we propose consensus promoter sequences for two distinct sigma factors. In addition to this, the gyr genes in M. tuberculosis, as in other species, are subject to autoregulation, albeit with slower kinetics, probably reflecting the slower metabolism of the organism.

Base Sequence↗