Expression levels influence ribosomal frameshifting at the tandem rare arginine codons AGG_AGG and AGA_AGA in Escherichia coli

Journal ArticleABSTRACT: The rare codons AGG and AGA comprise 2% and 4%, respectively, of the arginine codons of Escherichia coli K-12, and their cognate tRNAs are sparse. At tandem occurrences of either rare codon, the paucity of cognate aminoacyl tRNAs for the second codon of the pair facilitates peptidyl-tRNA shifting to the _x0001_1 frame. However, AGG_AGG and AGA_AGA are not underrepresented and occur 4 and 42 times, respectively, in E. coli genes. Searches for corresponding occurrences in other bacteria provide no strong support for the functional utilization of frameshifting at these sequences. All sequences tested in their native context showed 1.5 to 11% frameshifting when expressed from multicopy plasmids. A cassette with one of these sequences singly integrated into the chromosome in stringent cells gave 0.9% frameshifting in contrast to two- to four-times-higher values obtained from multicopy plasmids in stringent cells and eight-times-higher values in relaxed cells. Thus, _x0001_1 frameshifting efficiency at AGG_AGG and AGA_AGA is influenced by the mRNA expression level. These tandem rare codons do not occur in highly expressed mRNAs

Racial and Ethnic Disparities in Time to Cure of Incontinence Present at Nursing Home Admission

Abstract As many as half of older people that are admitted to nursing homes (NHs) are incontinent of urine and/or feces. Not much is known about the rate of cure of incontinence present at NH admission, but available reports suggest the rate is low. There have been racial and ethnic disparities in incontinence treatment, but the role of disparities in the cure of incontinence is understudied. Using the Peters-Belson method and multilevel predictors, our findings showed that there were disparities in the time to cure of incontinence for Hispanic NH admissions. A significantly smaller proportion of older Hispanic admissions were observed to have their incontinence cured and cured later than expected had they been White non-Hispanic. Reducing disparities in incontinence cure will improve health outcomes of Hispanic NH admissions. Significant predictors in our model suggest strategies to reduce the disparity including attention to managing fecal incontinence and incontinence in those with cognitive impairment, improving residents’ functional status, and increasing resources to NHs admitting older Hispanics with incontinence to develop innovative and cost effective ways to provide equitable quality care

Two groups of phenylalanine biosynthetic operon leader peptides genes: a high level of apparently incidental frameshifting in decoding Escherichia coli pheL

The bacterial pheL gene encodes the leader peptide for the phenylalanine biosynthetic operon. Translation of pheL mRNA controls transcription attenuation and, consequently, expression of the downstream pheA gene. Fifty-three unique pheL genes have been identified in sequenced genomes of the gamma subdivision. There are two groups of pheL genes, both of which are short and contain a run(s) of phenylalanine codons at an internal position. One group is somewhat diverse and features different termination and 5′-flanking codons. The other group, mostly restricted to Enterobacteria and including Escherichia coli pheL, has a conserved nucleotide sequence that ends with UUC_CCC_UGA. When these three codons in E. coli pheL mRNA are in the ribosomal E-, P- and A-sites, there is an unusually high level, 15%, of +1 ribosomal frameshifting due to features of the nascent peptide sequence that include the penultimate phenylalanine. This level increases to 60% with a natural, heterologous, nascent peptide stimulator. Nevertheless, studies with different tRNAPro mutants in Salmonella enterica suggest that frameshifting at the end of pheL does not influence expression of the downstream pheA. This finding of incidental, rather than utilized, frameshifting is cautionary for other studies of programmed frameshifting

Feasibility of Implementing a Tai Chi Program in an Assisted Living Facility: Reducing Fall Risks and Improving Quality of Life

One in four American older adults fall every year, resulting in injuries, death, and significant financial burden. Although fall etiology is multifactorial, the medical problems and aging factors that lead to unsteady gait and imbalance represent one of the major fall risks among older adults. A growing number of research studies support the health benefits of regular Tai Chi (TC) practice including improved physical, cognitive, and psychological function. The purpose of this quality improvement project was to assess the feasibility of establishing a 12-week (45 min per session) Tai Chi (TC) program (Sun Style Tai Chi) in a 75 bed assisted living facility as well as to evaluate the potential of the TC program to improve the fear of falling and functional mobility (as proxy for fall risk) and quality of life (QoL). A nurse who was a certified TC instructor taught the program. Twenty-three participants, 96% female and 96% white, mean (SD) age 83 (±7) years, attended one or more TC classes. Class attendance, self-reported questionnaires (e.g., fear of falling, QoL), and objective measure Timed Up and Go (TUG) were used to collect data. Nine participants (39%) completed 9 out of 12 sessions. Eleven participants (48%) completed both pre- and post-intervention measurements and twelve (52%) provided feedback on a post-intervention satisfaction survey. Participants showed 20% improvement in fear of falling (mean relative change) and 21% decrease (mean relative change) in TUG test (p = 0.001) with no clinically important changes in QoL. This quality improvement project suggested that TC is a feasible exercise that might have the potential to reduce risk of falls in older adults, and the program was well accepted with no serious or other adverse events reported. Further research studies are needed to examine the potential effects of TC programs with an appropriately powered RCT and longer intervention period

RECODE 2003

The RECODE database is a compilation of translational recoding events (programmed ribosomal frameshifting, codon redefinition and translational bypass). The database provides information about the genes utilizing these events for their expression, recoding sites, stimulatory sequences and other relevant information. The Database is freely available at http://recode.genetics.utah.edu/

Sequences that direct significant levels of frameshifting are frequent in coding regions of Escherichia coli

It is generally believed that significant ribosomal frameshifting during translation does not occur without a functional purpose. The distribution of two frameshift-prone sequences, A_AAA_AAG and CCC_TGA, in coding regions of Escherichia coli has been analyzed. Although a moderate level of selection against the first sequence is evident, 68 genes contain A_AAA_AAG and 19 contain CCC_TGA. The majority of those tested in their genomic context showed >1% frameshifting. Comparative sequence analysis was employed to assess a potential biological role for frameshifting in decoding these genes. Two new candidates, in pheL and ydaY, for utilized frameshifting have been identified in addition to those previously known in dnaX and nine insertion sequence elements. For the majority of the shift-prone sequences no functional role can be attributed to them, and the frameshifting is likely erroneous. However, none of frameshift sequences is in the 306 most highly expressed genes. The unexpected conclusion is that moderate frameshifting during expression of at least some other genes is not sufficiently harmful for cells to trigger strong negative evolutionary pressure