From RNA to DNA: Insights about the transition of informational molecule in the biological systems based on the structural proximity between the polymerases.

Structural relations in an evolutionary context of polymerases is crucial to gain insights into the transition from an RNA world to a Ribonucleoprotein world. Herein, we present a structural proximity tree for the polymerases, from which we observe that the enzymes that have RNA as substrate are more homogeneous than the group with DNA as substrate. The homogeneity observed in enzymes with RNA as a substrate, may be because they performed all steps in information processing. In this sense, the emergence of the DNA molecule posed new challenges to the biological systems, where several parts of the informational flow were individualized by the emergence of enzymes for each step. From the data presented, we propose a polymerase diversification model, in which we have RNA-dependent RNA polymerases as an ancestor and all other polymerases diverged directly from this group by a radiation process.

Identification and characterization of CircRNAs involved in the regulation of wheat root length.

BACKGROUND: Recent studies indicate that circular RNAs (circRNAs) may play important roles in the regulation of plant growth and development. Plant roots are the main organs of nutrient and water uptake. However, whether circRNAs involved in the regulation of plant root growth remains to be elucidated. METHODS: LH9, XN979 and YN29 are three Chinese wheat varieties with contrasting root lengths. Here, the root circRNA expression profiles of LH9, XN979 and YN29 were examined by using high-throughput sequencing technology. RESULTS: Thirty-three and twenty-two differentially expressed circRNAs (DECs) were identified in the YN29-LH9 comparison and YN29-XN979 comparison, respectively. Among them, ten DECs coexisted in both comparisons. As the roots of both LH9 and XN979 were significantly larger and deeper than YN29, the ten DECs coexisting in the two comparisons were highly likely to be involved in the regulation of wheat root length. Moreover, three of the ten DECs have potential miRNA binding sites. Real-time PCR analysis showed that the expression levels of the potential binding miRNAs exhibited significant differences between the long root plants and the short root plants. CONCLUSIONS: The expression levels of some circRNAs exhibited significant differences in wheat varieties with contrasting root phenotypes. Ten DECs involved in the regulation of wheat root length were successfully identified in which three of them have potential miRNAs binding sites. The expression levels of putative circRNA-binding miRNAs were correlated with their corresponding circRNAs. Our results provide new clues for studying the potential roles of circRNAs in the regulation of wheat root length.

Identification and characterization of CircRNAs involved in the regulation of wheat root length

BACKGROUND: Recent studies indicate that circular RNAs (circRNAs) may play important roles in the regulation of plant growth and development. Plant roots are the main organs of nutrient and water uptake. However, whether circRNAs involved in the regulation of plant root growth remains to be elucidated. METHODS: LH9, XN979 and YN29 are three Chinese wheat varieties with contrasting root lengths. Here, the root circRNA expression profiles of LH9, XN979 and YN29 were examined by using high-throughput sequencing technology. RESULTS: Thirty-three and twenty-two differentially expressed circRNAs (DECs) were identified in the YN29-LH9 comparison and YN29-XN979 comparison, respectively. Among them, ten DECs coexisted in both comparisons. As the roots of both LH9 and XN979 were significantly larger and deeper than YN29, the ten DECs coexisting in the two comparisons were highly likely to be involved in the regulation of wheat root length. Moreover, three of the ten DECs have potential miRNA binding sites. Real-time PCR analysis showed that the expression levels of the potential binding miRNAs exhibited significant differences between the long root plants and the short root plants. CONCLUSIONS: The expression levels of some circRNAs exhibited significant differences in wheat varieties with contrasting root phenotypes. Ten DECs involved in the regulation of wheat root length were successfully identified in which three of them have potential miRNAs binding sites. The expression levels of putative circRNA-binding miRNAs were correlated with their corresponding circRNAs. Our results provide new clues for studying the potential roles of circRNAs in the regulation of wheat root length.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge.

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/ß-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/ß-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Circular RNAs and exosomes in cancer: a mysterious connection.

Circular RNAs (CircRNAs) are a type of non-coding RNAs (NcRNAs) with a closed annular structure. Until next-generation sequencing (NGS) is developed, the misunderstanding of circRNAs 'splicing error' has changed, and the mysterious veil of circRNAs has been revealed. NGS provides an approach to investigate circRNAs. Many scholars point out that circRNAs may play an important role in many diseases, especially cancer. At the same time, exosomes, as a kind of extracellular vesicles loaded with many contents, are a hotspot in recent years. They can act as 'messengers' between cells, especially in cancer. Lately, it is interesting circRNAs are enriched and stable in exosomes, also called exo-circRNAs, and there have been several articles on circRNAs associated with exosomes. In this review, we summarize the characteristics of circRNAs, especially its main functions. Then, we briefly introduce exosomes and their function in cancer. Finally, the known relation between circRNAs and exosomes is discussed. With further researches, exo-circRNAs may be a novel pathway for cancer diagnosis and targeted therapy.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/β-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/β-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Circular RNAs are miRNA sponges and can be used as a new class of biomarker.

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that are involved in transcriptional and posttranscriptional gene expression regulation. The development of deep sequencing of ribosomal RNA (rRNA)-depleted RNA libraries, associated with improved computational tools, has provided the identification of several new circRNAs in all sorts of organisms, from protists, plants and fungi to animals. Recently, it was discovered that endogenous circRNAs can work as microRNA (miRNA) sponges. This means that the circRNAs bind to miRNAs and consequently repress their function, providing a new model of action for this class of ncRNA, as well as indicating another mechanism that regulates miRNA activity. As miRNAs control a large set of biological processes, circRNA sponge activity will also affect these pathways. Several studies have associated miRNA sponges with human diseases, including osteoarthritis, diabetes, neurodegenerative pathologies and several types of cancer. Additionally, high stability, abundance and tissue-specific expression patterns make circRNA sponges very attractive for clinical research. Herein, we review the biogenesis, properties and function of endogenous circRNA sponges, with a special focus on those related to human cancer. A list of web tools available for the study of circRNAs is also given. Additionally, we discuss the possibility of using circRNAs as molecular markers for the diagnosis of diseases.

Novel insights into the genetic and epigenetic paternal contribution to the human embryo.

The integrity of the sperm genome and epigenome are critical for normal embryonic development. The advent of assisted reproductive technology has led to an increased understanding of the role of sperm in fertilization and embryogenesis. During fertilization, the sperm transmits not only nuclear DNA to the oocyte but also activation factor, centrosomes, and a host of messenger RNA and microRNAs. This complex complement of microRNAs and other non-coding RNAs is believed to modify important post-fertilization events. Thus, the health of the sperm genome and epigenome is critical for improving assisted conception rates and the birth of healthy offspring.

Intranuclear network of 3-5 nm and 8-10 nm fibers in EL-4 lymphoma cells.

While much evidence indicates a high degree of spatial organization in the nucleus, the underlying molecular structures that support it remain poorly characterized. By extracting with high concentrations of RNase A in a modification of the sequential extraction protocol of Penman, we have identified a novel intranuclear network in the mouse lymphoma cell line, EL-4. Micrographs of embedment-free sections of extracted cells reveal anastomosing filaments of two different diameters: 3-5 nm and 8-10 nm. The 3-5-nm filaments are interconnected in many junctions and appear to blend smoothly into each other. The 8-10-nm fibers frequently split into two 3-5-nm filaments. Some 3-5-nm fibers appear to be connected at 90 degrees angles with the 8-10-nm fibers. All junctions are smooth with no apparent junction protein. Flow cytometric analysis of RNase A- (and DNase I-) extracted nuclear matrices indicates that they do not contain significant amounts of protein that react with anti-actin and anti-vimentin monoclonal antibodies. Extraction of EL-4 nuclear matrices with high salt does not reveal 8-10-nm core filaments described after similar treatment of tumor cell lines of cervical and mammary origin. The novel characteristics of the core filaments in EL-4 lymphoma cells may reflect cell-type specificity of the nuclear matrix.

El surgimiento de la biología molecular / Appearance of molecular biology

La biología molecular constituye hoy en día la punta de lanza dentro de las perspectivas diagnósticas y terapéuticas para el próximo milenio. Ni el médico clínico ni el investigador biomédico pueden permanecer ajenos a dichos acontecimientos, es por ello que hemos considerado importante revisar los aspectos sobresalientes y prácticos de esta rama de la ciencia, a través de una serie de artículos que hagan más familiar su comprensión, fundamentalmente para aquellos quienes no tienen acceso a la información especializada

Heart induction in wild-type and cardiac mutant axolotls (Ambystoma mexicanum).

We have re-examined some of the factors affecting the induction of heart-forming mesoderm in the axolotl. The formation of functional, rhythmically contracting myocardial tissue was used as an assay. We have found that heart-forming mesoderm is fully induced and capable of completing its developmental repertoire by the end of neurulation. As has been previously reported, pharyngeal endoderm appears to be the major inductor of heart mesoderm. Unlike previous workers, we have found that the inducing activity appears to be highly localized in the mid-ventral pharyngeal endoderm. The endoderm retains its inductive properties, and the mesoderm retains at least some capacity to respond, long after the heart-forming mesoderm is apparently fully induced. We have also found that RNA extracts from pharyngeal endoderm, which are capable of causing cardiac-lethal (c/c) mutant axolotl hearts to begin beating, are not capable of inducing early wild-type heart-forming mesoderm. Based on these results, we speculate that induction of heart-forming mesoderm is a two-step process. The first signal, occurring during neurulation, directs the mesoderm to begin differentiating into cardiomyocytes, and the second, beginning in mid- to late neurulation and continuing until just prior to the onset of heartbeat, causes myofibrillogenesis and the initiation of rhythmic contractions. The latter signal, which is lacking in c/c mutant embryos, appears to be necessary to override an inhibition present in the embryonic milieu.

Acido ribonucleico, inmunidad y leucemia murina / Ribonucleic acid, immunity and murine leukemia

Los numerosos estudios realizados con ARN "inmune" en distintas especies animales y los éxitos logrados en este campo nos sugirieron la idea de ensayar un modelo similar en las leucemias y tumores que mantenemos en la cepa de ratones BALB, en nuestro laboratorio. El ARN extraído del bazo de ratones alogeneicos previamente inmunizados contra dichos tumores y leucemias no mostró ser capaz de inducir ningún grado de inmunidad al ser inoculado a ratones BALB. Sin embargo, nos llamó la atención que ratones BALB inoculados simultáneamente con ARN de bazo o hígado normal con el fin de descartar efectos inespecíficos, morían en mayor proporción que los testigos. Como estos resultados se repitieron en varias oportunidades, decidimos investigar cual podría ser el efecto del ARN normal sobre el desarrollo de una neoplasia murina. Se estudio la influencia del ARN murino de bazo e hígado normal en el desarrollo de una leucemia, H110, inducida en ratones mediante material neoplásico humano, y que se mantiene en la cepa BALB por pasajes celulares seriados. El ARN obtenido por extracción fenólica y analizados mediante técnicas físicas y químicas demostró estar formado aparentemente por ARN de tipo ribosomal y de transferencia, presentar buenas condiciones de polimerización y poca contaminación. Experimentos realizados "in vivo" mostraron que el ARN de hígado normal, en dosis de 5 mg, inoculado 10 días antes del desafío con 40 células leucémicas H110 (LD50) llevó al desarrollo de leucemia en el 100 por ciento de los animales tratados, en un lapso promedio de 17 días, mientras que la incidencia de leucemia en los controles fue del 52 por ciento con una latencia promedio de 24 días. Las diferencias observadas fueron estadísticamente significativas... (TRUNCADO)(AU)