Shiu lab identifies novel players in gene silencing mechanism
May 23, 2013
Many organisms, including humans, maintain cellular mechanisms for detecting and silencing, or “turning off,” problematic genes. These silencing mechanisms are an important defense against intruders such as viruses and transposons (genetic elements that jump around in the genome). The fungus Neurospora crassa has an efficient mechanism to detect mishaps that occur when genes are unpaired during sexual reproduction (i.e., genes that are present in only one of the two parents), in a process called meiotic silencing by unpaired DNA (MSUD). In two articles in the May 2013 issue of Genetics, the Shiu lab identifies novel players in this process, including small RNAs and the first nuclear MSUD protein.
Dissecting the genetic components of MSUD in N. crassa involves a combination of advanced genetic and genomic techniques. In this study, the scientists used a reverse genetics technique to identify two genes that are required for the MSUD mechanism. Strains of N. crassa lacking either gene are unable to silence unpaired DNA. The two genes, named suppressor of ascus dominance-4 and -5 (sad-4 and sad-5), were subsequently sequenced and characterized using various cellular and genetic experimental approaches. The scientists also employed a high-throughput sequencing technique, known as Illumina sequencing, to detect and characterize small RNAs produced during MSUD. There are many novel findings in these combined studies. SAD-4 and SAD-5 are the first proteins identified in MSUD that are not required for sporulation, “providing the first indication that MSUD is not necessarily coupled to sexual development.” SAD-5 is also the first nuclear protein to be identified in this silencing process. Its location, state the authors, “makes it tempting to speculate that it may be directly involved in the initial stages of MSUD.” The researchers also provide the first direct evidence of the involvement of small RNAs in the process.
Elucidating how this gene silencing mechanism works in fungi may shed light on similar genetic defense mechanisms in higher organisms, including humans. Furthermore, the mechanism for “shutting off” undesirable genes has applications in a number of areas, including the pharmaceutical industry and agriculture.
Thomas Hammond, the lead author of the two studies, did his postdoctoral work in the Shiu lab from 2007 to 2012 and is now an assistant professor at Illinois State University. Other coauthors from the Shiu lab include Seung Ah Lee (undergraduate), Hua Xiao (postdoc), Erin Boone, and Logan Decker (graduate students).
This work was supported by funding from the National Science Foundation.
The two reports, titled “Identification of small RNAs associated with meiotic silencing by unpaired DNA” and “Novel proteins required for meiotic silencing by unpaired DNA and siRNA generation in Neurospora crassa,” are available in the May 2013 issue of Genetics.
Written by: Melody Kroll
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