Tuesday, January 29, 2019

Super-Mendelian inheritance mediated by CRISPR–Cas9

A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems have recently been developed in insects, which leverage the sequence-targeted DNA cleavage activity of CRISPR–Cas9 and endogenous homology-directed repair mechanisms to convert heterozygous genotypes to homozygosity. If implemented in laboratory rodents, similar systems would enable the rapid assembly of currently impractical genotypes that involve multiple homozygous genes (for example, to model multigenic human diseases). However, such a system has not yet been demonstrated in mammals. Here  an active genetic element that encodes a guide RNA, which is embedded in the mouse tyrosinase (Tyr) gene, is used  to evaluate whether targeted gene conversion can occur when CRISPR–Cas9 is active in the early embryo or in the developing germline. Although Cas9 efficiently induces double-stranded DNA breaks in the early embryo and male germline, these breaks are not corrected by homology-directed repair. By contrast, Cas9 expression limited to the female germline induces double-stranded breaks that are corrected by homology-directed repair, which copies the active genetic element from the donor to the receiver chromosome and increases its rate of inheritance in the next generation. These results demonstrate the feasibility of CRISPR–Cas9-mediated systems that bias inheritance of desired alleles in mice and that have the potential to transform the use of rodent models in basic and biomedical research.


Sunday, January 20, 2019

Plants fight fungi using kiwellin proteins

Fungal pathogens of plants  often secrete proteins that aid growth and reproduction in the host. These are termed effector proteins, and some are deregulated metabolic enzymes that manipulate key metabolic pathways in plants. A new protein has been identified in maize which  blocks the enzymatic activity of a fungal effector enzyme, thereby thwarting the effector’s ability to influence maize metabolism in a way that limits the plant’s defence response.
For more details: https://www.nature.com/articles/d41586-019-00092-2


Introns are ubiquitous features of all eukaryotic cells. Introns need to be removed from nascent messenger RNA through the process of splicing to produce functional proteins.Physical presence of introns in the genome promotes cell survival under starvation conditions. A systematic deletion set of all known introns in budding yeast genes indicates that, in most cases, cells with an intron deletion are impaired when nutrients are depleted. This effect of introns on growth is not linked to the expression of the host gene, and was reproduced even when translation of the host mRNA was blocked. Transcriptomic and genetic analyses indicate that introns promote resistance to starvation by enhancing the repression of ribosomal protein genes that are downstream of the nutrient-sensing TORC1 and PKA pathways.