The expression of tubulin cofactor A (TBCA) is regulated by a noncoding antisense Tbca RNA during testis maturation

Abstract - Recently, long noncoding RNAs have emerged as pivotal molecules for the regulation of coding genes' expression. These molecules might result from antisense transcription of functional genes originating natural antisense transcripts (NATs) or from transcriptional active pseudogenes. TBCA interacts with β-tubulin and is involved in the folding and dimerization of new tubulin heterodimers, the building blocks of microtubules. Methodology/Principal findings: We found that the mouse genome contains two structurally distinct Tbca genes located in chromosomes 13 (Tbca13) and 16 (Tbca16). Interestingly, the two Tbca genes albeit ubiquitously expressed, present differential expression during mouse testis maturation. In fact, as testis maturation progresses Tbca13 mRNA levels increase progressively, while Tbca16 mRNA levels decrease. This suggests a regulatory mechanism between the two genes and prompted us to investigate the presence of the two proteins. However, using tandem mass spectrometry we were unable to identify the TBCA16 protein in testis extracts even in those corresponding to the maturation step with the highest levels of Tbca16 transcripts. These puzzling results led us to re-analyze the expression of Tbca16. We then detected that Tbca16 transcription produces sense and natural antisense transcripts. Strikingly, the specific depletion by RNAi of these transcripts leads to an increase of Tbca13 transcript levels in a mouse spermatocyte cell line. Conclusions/Significance: Our results demonstrate that Tbca13 mRNA levels are post-transcriptionally regulated by the sense and natural antisense Tbca16 mRNA levels. We propose that this regulatory mechanism operates during spermatogenesis, a process that involves microtubule rearrangements, the assembly of specific microtubule structures and requires critical TBCA levels.

Convective patterns under the Indo-Atlantic << box >>

Using fluid mechanics, we reinterpret the mantle images obtained from global and regional tomography together with geochemical, geological and paleomagnetic observations, and attempt to unravel the pattern of convection in the Indo-Atlantic "box" and its temporal evolution over the last 260 Myr. The << box >> presently contains a) a broad slow seismic anomaly at the CMB which has a shape similar to Pangea 250 Myr ago, and which divides into several branches higher in the lower mantle, b) a "superswell, centered on the western edge of South Africa, c) at least 6 "primary hotspots" with long tracks related to traps, and d) numerous smaller hotspots. In the last 260 Myr, this mantle box has undergone 10 trap events, 7 of them related to continental breakup. Several of these past events are spatially correlated with present-day seismic anomalies and/or upwellings. Laboratory experiments show that superswells, long-lived hotspot tracks and traps may represent three evolutionary stages of the same phenomenon, i.e. episodic destabilization of a hot, chemically heterogeneous thermal boundary layer, close to the bottom of the mantle. When scaled to the Earth's mantle, its recurrence time is on the order of 100-200 Myr. At any given time, the Indo-Atlantic box should contain 3 to 9 of these instabilities at different stages of their development, in agreement with observations. The return flow of the downwelling slabs, although confined to two main << boxes >> (Indo-Atlantic and Pacific) by subduction zone geometry, may therefore not be passive, but rather take the form of active thermochemical instabilities. (c) 2005 Elsevier B.V. All rights reserved.