Papers by Aarti Sahasranaman
The EMBO Journal, 2011
The precise functions of most of the ∼200 assembly factors and 79 ribosomal proteins required to ... more The precise functions of most of the ∼200 assembly factors and 79 ribosomal proteins required to construct yeast ribosomes in vivo remain largely unexplored. To better understand the roles of these proteins and the mechanisms driving ribosome biogenesis, we examined in detail one step in 60S ribosomal subunit assembly-processing of 27SA(3) pre-rRNA. Six of seven assembly factors required for this step (A(3) factors) are mutually interdependent for association with preribosomes. These A(3) factors are required to recruit Rrp17, one of three exonucleases required for this processing step. In the absence of A(3) factors, four ribosomal proteins adjacent to each other, rpL17, rpL26, rpL35, and rpL37, fail to assemble, and preribosomes are turned over by Rat1. We conclude that formation of a neighbourhood in preribosomes containing the A(3) factors establishes and maintains stability of functional preribosomes containing 27S pre-rRNAs. In the absence of these assembly factors, at least one exonuclease can switch from processing to turnover of pre-rRNA.
Molecular Biology of the Cell, 2008
In Saccharomyces cerevisiae, more than 180 assembly factors associate with preribosomes to enable... more In Saccharomyces cerevisiae, more than 180 assembly factors associate with preribosomes to enable folding of pre-rRNA, recruitment of ribosomal proteins, and processing of pre-rRNAs to produce mature ribosomes. To examine the molecular architecture of preribosomes and to connect this structure to functions of each assembly factor, assembly subcomplexes have been purified from preribosomal particles. The Nop7-subcomplex contains three assembly factors: Nop7, Erb1, and Ytm1, each of which is necessary for conversion of 27SA 3 pre-rRNA to 27SB S pre-rRNA. However, interactions among these three proteins and mechanisms of their recruitment and function in pre-rRNPs are poorly understood. Here we show that Ytm1, Erb1, and Nop7 assemble into preribosomes in an interdependent manner. We identified which domains within Ytm1, Erb1, and Nop7 are necessary for their interaction with each other and are sufficient for recruitment of each protein into preribosomes. Dominant negative effects on growth and ribosome biogenesis caused by overexpressing truncated Ytm1, Erb1, or Nop7 constructs, and recessive phenotypes of the truncated proteins revealed not only interaction domains but also other domains potentially important for each protein to function in ribosome biogenesis. Our data suggest a model for the architecture of the Nop7-subcomplex and provide potential functions of domains of each protein.
Molecular and Cellular Biology, 2014
Previous work from our lab suggests that a group of interdependent assembly factors (A(3) factors... more Previous work from our lab suggests that a group of interdependent assembly factors (A(3) factors) is necessary to create early, stable preribosomes. Many of these proteins bind at or near internal transcribed spacer 2 (ITS2), but in their absence, ITS1 is not removed from rRNA, suggesting long-range communication between these two spacers. By comparing the nonessential assembly factors Nop12 and Pwp1, we show that misfolding of rRNA is sufficient to perturb early steps of biogenesis, but it is the lack of A(3) factors that results in turnover of early preribosomes. Deletion of NOP12 significantly inhibits 27SA(3) pre-rRNA processing, even though the A(3) factors are present in preribosomes. Furthermore, pre-rRNAs are stable, indicating that the block in processing is not sufficient to trigger turnover. This is in contrast to the absence of Pwp1, in which the A(3) factors are not present and pre-rRNAs are unstable. In vivo RNA structure probing revealed that the pre-rRNA processing defects are due to misfolding of 5.8S rRNA. In the absence of Nop12 and Pwp1, rRNA helix 5 is not stably formed. Interestingly, the absence of Nop12 results in the formation of an alternative yet unproductive helix 5 when cells are grown at low temperatures.
Contemporary Clinical Trials, 2015
Non-communicable diseases (NCDs) are emerging as the predominant global health challenge of this ... more Non-communicable diseases (NCDs) are emerging as the predominant global health challenge of this century. Physical inactivity is one of the primary risk factors for NCDs. Therefore, increasing physical activity levels is a public health imperative. The arrival of affordable wearable technologies, such as wireless pedometers, provides one strategy for encouraging walking. However, the effectiveness of these technologies in promoting sustained behavior change has not been established. Insights from economics suggest that incentives may be a useful strategy for increasing maintenance and effectiveness of behavior change interventions, including physical activity interventions that rely on wearable technologies. The aim of this trial is to test the effectiveness of a common wireless pedometer with or without one of two types of incentives (cash or donations to charity) for reaching weekly physical activity goals. We present here the design and baseline characteristics of participants of this four arm randomized controlled trial. 800 full-time employees (desk-bound office workers) belonging to 15 different worksites (on average, 53 (sd: 37) employees at each worksite) were successfully randomized to one of four study arms. If shown to be effective, wearable technologies in concert with financial incentives may provide a scalable and affordable health promotion strategy for governments and employers seeking to increase the physical activity levels of their constituents.
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Papers by Aarti Sahasranaman