Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe.

RNA-binding proteins play a key role in post-transcriptional regulation of mRNA stability and translation. We have identified that RBM3, a translation regulatory protein, is significantly upregulated in human tumors, including a stage-dependent increase in colorectal tumors. Forced RBM3 overexpression in NIH3T3 mouse fibroblasts and SW480 human colon epithelial cells increases cell proliferation and development of compact multicellular spheroids in soft agar suggesting the ability to induce anchorage-independent growth. In contrast, downregulating RBM3 in HCT116 colon cancer cells with specific siRNA decreases cell growth in culture, which was partially overcome when treated with prostaglandin E(2), a product of cyclooxygenase (COX)-2 enzyme activity. Knockdown also resulted in the growth arrest of tumor xenografts. We have also identified that RBM3 knockdown increases caspase-mediated apoptosis coupled with nuclear cyclin B1, and phosphorylated Cdc25c, Chk1 and Chk2 kinases, implying that under conditions of RBM3 downregulation, cells undergo mitotic catastrophe. RBM3 enhances COX-2, IL-8 and VEGF mRNA stability and translation. Conversely, RBM3 knockdown results in loss in the translation of these transcripts. These data demonstrate that the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis.

Maternal transfer of melatonin alters the growth and sexual maturation of young Indian palm squirrel Funambulus pennanti.

To date, the phenomenon of maternal transfer of hormones to the young is an enigma. The present study explains for the first time the maternal transfer of melatonin (MEL) to the young, affecting neonatal growth and sexual maturation. The suckling pups of MEL-treated mothers exhibited significant decreases in body, testicular, vas deferens (male pups), ovarian and uterine (female pups) weights and increases in pineal gland activity along with high plasma MEL levels. The plasma level of testosterone decreased significantly in male pups, while estradiol increased and progesterone decreased in female pups of MEL-treated mothers. These results clearly suggest that MEL could be transported from the mothers to their young postnatally via the milk in order to influence neonatal growth and sexual maturation. Our results support the earlier concept and show for the first time that MEL can be transported from the mother to the young either prenatally through the placenta or postnatally via the milk. Therefore, maternal MEL can act as a biological signal for neonatal growth and sexual maturation.

Comparative view of pineal gland morphology of nocturnal and diurnal birds of tropical origin.

Although having a similar developmental pattern, the pineal gland of tropical birds varies in shape, size, and morphology, probably more than any other part of the avian brain. Following the old classification, we noted a solid follicular (transitional) type of the pineal gland in the nocturnal bird Athene brama, and a tubulo-follicular and elongated tubular types of pineal gland in diurnal birds Perdicula asiatica and Euroloncha punchulata, respectively. Detailed light (LM) and electron microscopic (EM) studies of the pineal gland from these tropical birds revealed the presence of a well-developed, functionally active gland in nocturnal birds (contrary to reports available until now). Unlike diurnal birds, the nocturnal bird A. brama has no deep pineal in the posterior region (near the habenular commissure). It could be that the deep encephalic receptors have no/fewer functions in nocturnal birds. At present, we were unable to define the significance of deep pineal in these tropical avian species. A notable difference in the proximodistal orientation of intrapineal follicles and parenchymatous cells was noted among these birds due to different habitats. Ultrastructurally, the pinealocytes exhibited great similarities in terms of secretory organelles, except for the presence of some peculiar membranous structure in E. punchulata. The pinealocytes have rudimentary photoreceptive features (e.g., outer segment) along with cytoplasmic organelles for secretory activity, suggesting both photosensory and photosecretory types of function. The present study also suggests more heterogenicity in pineal gland morphology (cellular architecture) among diurnal birds than the nocturnal one.

Impact of photoperiodic exposures during late gestation and lactation periods on the pineal and reproductive physiology of the Indian palm squirrel, Funambulus pennanti.

Studies on the maternal transfer of photoperiodic information in mammals indicate that the daily photoperiod perceived by the mother during the gestation-lactation period is communicated to the fetus either through the placenta or via the milk. However, the impact of photoperiodic exposures during gestation and lactation on the maternal pineal and reproductive physiology has not been reported for any tropical rodent. The exposure of pregnant female Indian palm squirrels (Funambulus pennanti) to constant light (24 h light:0 h dark), constant dark (0 h light:24 h dark), long daylength (14 h light:10 h dark) or short daylength (10 h light:14 h dark) during early gestation (< 30 days) resulted in the resorption of pregnancy, while during late gestation (> 30 days), it did not interfere with the maintenance of pregnancy. Alterations in photoperiodic condition during late gestation and lactation altered the postpartum recovery process. Pineal gland activity, as assessed by pineal mass, protein content and plasma melatonin, was lowest during the breeding phase, but increased gradually after parturition until the next breeding phase. During gestation and lactation, constant light, long daylength and short daylength conditions were less effective, while constant dark condition had a profound effect in depressing pineal gland activity, which subsequently advanced postpartum recovery. Hence, lactating females under constant darkness prepare themselves for next mating much earlier than females under natural daylength (12 h light:12 h dark) conditions. Therefore, photoperiodic information, mediated via the pineal gland, may be important for maintaining gestation physiology as well as postpartum recovery in female rodents.

Profile of organ weights and plasma concentrations of melatonin, estradiol and progesterone during gestation and post-parturition periods in female Indian palm squirrel Funambulus pennanti.

Todate, report about the role of pineal gland in maintaining the normal physiology of gestation is scanty. Present study is the first of its kind giving a detail profile of organ weights and plasma concentration of melatonin, estradiol and progesterone to suggest a possible role of pineal gland in maintaining normal physiology during gestation and post-parturition periods of female Indian palm squirrel F. pennanti. Inspite of, inverse pineal-gonadal/melatonin-steroids interrelationship in adult (non-pregnant) females, the present results study suggest a direct relationship of pineal gland activity with ovarian steroids especially during the gestation period. The inverse relationship of melatonin and ovarian steroids is again established after parturition and maintained throughout the life. Thus the pineal gland (activity as judged by its weight, biochemical contents i.e. protein and cholesterol and plasma melatonin level) maintained ovarian/uterine physiology and regulated plasma concentrations of estradiol and progesterone during gestation and post-parturition periods. It is suggested that the pineal gland and its hormone melatonin play an important role to maintain the normal physiology of gestation and the post-partum recovery in Indian palm squirrel F. pennanti.

Maternal photoperiodic exposures alter the neonatal growth, pineal functions and sexual development of the Indian palm squirrel F. pennanti. Short communication.

The phenomenon of maternal transfer of photic information to their young ones is still an enigma. Existing reports in some rodents of temperate zone suggest that photoperiodic condition experienced by mother during their gestation period influences the pineal physiology of fetus, but nothing has been reported about the growth and sexual development of pups. Present experiment for the first time explains the effect of gestational photoperiod on the growth and sexual development of pups from a seasonally breeding tropical rodent F. pennanti. The results suggest that, constant light (LL; 24L: OD) and long day length (LDL; 14L: 10D) experiencing mother conveyed the photic information to young ones to inhibit the pineal function, while short day length (SDL; 10L: 14D) stimulated the pineal function in pups. Altered pineal functions of pups ultimately interfered with their growth and sexual maturation. Most interestingly, the pups delivered by DD experiencing mothers and then reared under same condition, at the age of 40 days attained a level of growth and sexual maturity equivalent to the growth and sexual maturation of 60 days old pups under natural day length (NDL) condition. Therefore, we may suggest that the photic information perceived by the mother alter her normal melatonin level, hence, passing through placenta melatonin influences the growth and sexual maturation of the young ones.