Nearly 5 percent of the human genome codes for proteins, and scientists are only beginning to understand the role of the rest of the "non-coding" genome. Among the least studied non-coding genes – which are transcribed from DNA to RNA but generally are not translated into proteins – are the long non-coding RNAs (lncRNAs).
Before the human genome was fully sequenced, it was a "protein-centric world," said University of Illinois cell and developmental biology professor Kannanganattu Prasanth, who led the study. With the sequencing of the genome it became clear, however, that a majority of genes code for RNAs that are not translated into proteins.
In recent years, research on non-coding RNAs has blossomed, but most studies have focused only on small non-coding RNAs, which play critical roles in several aspects of cellular function. There have been comparatively fewer studies on lncRNAs, Prasanth said. As a result, researchers are only beginning to understand the functions of a few lncRNAs.
Prasanth's laboratory focuses on understanding the role of lncRNAs, such as MALAT1, which normally are distributed in the nucleus of mammalian cells.
Preliminary studies suggest that lncRNAs carry out vital regulatory functions in cells. When those functions go awry, Prasanth said, serious consequences can result. Abnormal expression of the MALAT1 gene, for example, is implicated in many cancers, including breast, lung and liver cancers, "so the scientific world was interested in what this RNA could be doing in normal cells, and how changes in its expression correlate with cancer," he said.
Prasanth was also the co-first-author of another study, recently published in The EMBO Journal, that found that MALAT1 plays a role in recruiting important proteins, called pre-mRNA splicing factors, to the site of gene transcription in the nucleus.
Pre-mRNA splicing involves cutting out unneeded sequences and piecing the mRNAs together before they are exported from the nucleus and translated into proteins.
"That study gave us the clue that MALAT1 is an important gene that might be involved in pre-mRNA metabolism," Prasanth said.
In the new study, Prasanth and his colleagues tested the hypothesis that MALAT1 interacts with and modulates the behavior of a group of pre-mRNA splicing factors known as the SR-family splicing factors.
The researchers found that the MALAT1 sequence contains multiple regions that can bind SR-splicing proteins. Further experiments showed that MALAT1 does indeed bind to several members of the SR-proteins the team analyzed.
Furthermore, depleting cells of MALAT1 or over-expressing the splicing factors to which it can bind led to the same alteration in the splicing of a large number of pre-mRNAs in the cells, suggesting that MALAT1 latches onto the splicing factors and regulates their access to new transcripts.
"All of the data strongly suggest that MALAT1 is acting as a regulator of splicing by modulating the levels of the splicing factors in the cell," Prasanth said.
This study verifies that MALAT1 plays a key role in pre-mRNA processing, with broad implications for human health, Prasanth said.
"Numerous studies have shown that aberrant splicing of pre-mRNA is a major issue associated with several diseases, including cancer," he said. "Some of the factors we know interact with MALAT1 have been shown to be oncogenes. If you over-express these genes you can make a cell cancerous."
"Similarly, some of the genes whose pre-mRNA splicing is controlled by MALAT1 are members of the cancer 'signature genes,' " Prasanth said. "This means that their abnormal expression is directly correlated with several cancers."
Post-doctoral researcher Vidisha Tripathi led this work, with assistance from undergraduate student David Song. Supriya Prasanth, a professor of cell and developmental biology at Illinois, and her graduate student, Zhen Shen, also contributed to the study. The research team also included scientists from the University of Toronto; ISIS Pharmaceuticals, Carlsbad, Calif.; and Wright State University, Dayton, Ohio.Editor's notes: To reach Kannanganattu Prasanth, e-mail
Diana Yates | EurekAlert!
Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology
Scientists generate an atlas of the human genome using stem cells
24.04.2018 | The Hebrew University of Jerusalem
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
24.04.2018 | Life Sciences
24.04.2018 | Materials Sciences
24.04.2018 | Trade Fair News