Preprint: Ravikumar S, Devanapally S, Jose AM. Gene silencing by double-stranded RNA from C. elegans neurons reveals functional mosaicism of RNA interference. Online Aug 16, 2018, BioRxiv. Download pdf.
This study reveals random variation in the mechanism(s) used for RNA interference. We found that dsRNA from neurons can silence cells throughout the animal using a mechanism that can differ from that used by other sources of dsRNA. Single-cell resolution measurements of silencing revealed that the identities of intestinal cells requiring a particular mechanism can vary from animal to animal. This is an illustration of functional mosaicism, whereby the same function - gene silencing - is achieved through different mechanisms in different cells.
Preprint: Devanapally S, Allgood S, Jose AM. Mating can cause transgenerational gene silencing in Caenorhabditis elegans. Online Jun 11, 2017, BioRxiv. Download pdf.
This study reveals the existence of a mechanism that maintains gene silencing initiated upon ancestral mating. Such mating-induced silencing can last for >150 generations and thereby allow retention of even detrimental sequences acquired through mating, creating a reservoir of sequences that contribute to novelty when activated during evolution. Loci that are subject to such transgenerational gene silencing are useful for discovering non-genetic aspects of the cell code that perpetuates life.
2018: Jose AM. Replicating and cycling stores of information perpetuate life. BioEssays. 40(4):1700161. (Online on 6/14/2017 with revisions on 7/30/2017 and 8/26/2017, BioRxiv) See video abstract, Download pdf. [Inside front cover]
This essay integrates insights from the history of biology to bring into sharp relief what we do not know about the fundamental nature of living things: all the information that is necessary to perpetuate life. Information is held within cells in two distinct forms: (1) the well-studied genome sequence; and (2) the under-explored changing arrangement of all molecules within a cell that return to a similar configuration at the start of each generation. Together, they form the cell code - the interdependent and coevolving arrangement of molecules that perpetuates the organism. While we do not know the entire cell code of any organism, clearly seeing the relationship between an organism and its cell code has broad implications for our understanding of evolution, the origins of inherited diseases, and the potential synthesis of living things.
2017: Raman P, Zaghab S, Traver EC, Jose AM. The double-stranded RNA binding protein RDE-4 can act cell autonomously during feeding RNAi in C. elegans. Nucleic Acids Research. 45(14):8463-73. (Online on 12/2/2016, BioRxiv) Download pdf.
This study analyzes the organismal fate of ingested dsRNA and discovers the general reduction in silencing by ingested dsRNA that occurs within cells that express repetitive DNA.
2017: Choi YS, Edwards LO, DiBello A, Jose AM. Removing bias against short sequences enables northern blotting to better complement RNA-seq for the study of small RNAs. Nucleic Acids Research. 45(10):e87. (Online on 8/16/2016, BioRxiv) Download pdf.
This study highlights the need for approaches that complement RNA-seq, discovers that northern blotting of small RNAs is biased against short sequences, and develops a protocol that removes this bias.
2016: Marré JA, Traver EC, Jose AM. Extracellular RNA is transported from one generation to the next in C. elegans. Proceedings of the National Academy of Sciences USA. 113(44):12496-501. Download pdf. [Also see 2017: Marré J and Jose A. Inheritance of extracellular nutrition and information in Caenorhabditis elegans. Mol. Reprod. Dev. 84(4):283. Download pdf.]
This study demonstrates that extracellular RNA from a parent can be imported into oocytes, be held within intracellular vesicles, and reach progeny to cause gene silencing. This work was highlighted in This Week in PNAS. News reports on this work were published on many websites including BioTechniques News, University of Maryland's website, Epigenie.com, LabRoots.com, and Genetic Engineering & Biotechnology News.
2016: Le HH, Looney M, Strauss B, Bloodgood M, Jose AM. Tissue homogeneity requires inhibition of unequal gene silencing during development. Journal of Cell Biology. 214(3):319-31. Download pdf.
This study develops a paradigm for answering the fundamental question: given the numerous components of a cell, how do animals keep any two cells equal? As part fo this study, we collaborated with a computer scientist from Center for Advanced Study of Language (Dr. Michael Bloodgood) for the use of machine learning approaches. This work was highlighted as the In Focus article of the issue. News reports on this work were published on many websites including University of Maryland's website.
2016: Blumenfeld AL, Jose AM. Reproducible features of small RNAs in C. elegans reveal NU RNAs and provide insights into 22G RNAs and 26G RNAs. RNA. 22:184-92 Download pdf.
This study analyzes small RNAs in C. elegans, identifies a class of RNAs smaller than 18 nucleotides called NU RNAs (pronounced "new RNAs"), and makes the case for RNAs smaller than 18 nucleotides being used for sequence-specific gene regulation. PACER (Programs for Analysis of C. elegans small RNAs) is a collection of all the scripts and programs used in this paper and wrapped by Rex Ledesma.
2015: Jose AM. Movement of regulatory RNA between animal cells. genesis. 53(7): 395-416. Download pdf.
This invited review summarizes the state of the field, highlights unanswered questions, and suggests future directions.
2015: Devanapally S, Ravikumar S, Jose AM. Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing. Proceedings of the National Academy of Sciences USA. 112(7):2133-8. Download pdf.
This study demonstrates for the first time the transport of sequence-specific information from neurons to germ cells in an animal. This work was highlighted in This Week in PNAS and Science Signaling. News reports on this work were published on many websites including University of Maryland's website, the Diamondback newspaper, Epigenie.com, and Biomedical picture of the day.
2012: Jose AM*, Kim YA*, Leal-Ekman S, Hunter CP. A conserved tyrosine kinase promotes the import of silencing RNAs into C. elegans cells. Proceedings of the National Academy of Sciences USA. 109(36):14520-5.*equal contribution. Download pdf.
This study demonstrates that the import of RNA into animal cells is regulated by a conserved tyrosine kinase that likely responds to environmental changes. Undergraduate Yunsoo Kim won the Henderson prize and the Hoopes prize for her thesis as part of this work.
2011: Jose AM, Garcia GA, Hunter CP. Two classes of silencing RNAs move between C. elegans tissues. Nature Structural and Molecular Biology. 18(11): 1184-8. Download pdf.
This study deduces the possible molecular identities of mobile RNAs. A news report on this work was published in the Harvard Gazette. The significance and commercial applicability of this work is highlighted at Harvard University's website.
2009: Jose AM, Smith JJ, Hunter CP. Export of RNA silencing from C. elegans tissues does not require the RNA channel SID-1. Proceedings of the National Academy of Sciences USA. 106(7): 2283-8. Download pdf.
This study establishes the generality of RNA transport between C. elegans cells and uncovers the existence of novel pathways that make and export mobile RNA. Description for the general public is available at Harvard University's website.