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Abstract.
To better understand the genetic controls of leaf senescence, a tobacco (
Nicotiana tabacum
L. cv.SR1) mRNA that is up-regulated during senescencewas isolated by the cDNA-ampli®ed restriction frag-ment polymorphism method and the cDNA wascloned. The mRNA coded for the early light-inducedprotein (ELIP), a member of the chlorophyll a/b-binding protein family that has been implicated inassembly or repair of the photosynthetic machineryduring early chloroplast development and abiotic stress.A protein antigenically recognized by antibodies toELIP appeared during senescence with kinetics similarto those of its mRNA. The mRNA, designated ELIP-TOB, was detected earlier when senescence was en-hanced by leaf detachment and treatment with 1-ami-no-cyclopropane-1-carboxylic acid, and was detectedlater when senescence was retarded by benzyladenine.However, no ELIP-TOB mRNA was seen in the darkeven though senescence was accelerated under theseconditions. Furthermore, water stress and anaerobiosisstimulated the appearance of ELIP-TOB mRNA beforelosses of chlorophyll could be detected. We discuss theconditions that may lead to the up-regulation of ELIP-TOB during senescence and speculate as to the role of the gene product in this terminal phase of leadevelopment.
Key words:
Abiotic stress ± Chloroplast ± Early light-induced protein ± 
Nicotiana
(leaf senescence) ± Senescence
Introduction
Leaf senescence, the ®nal stage of leaf development, iscontrolled in part by a program involving gene expres-sion (Becker and Apel 1993; Buchanan-Wollaston 1997;Smart 1994; Humbeck et al. 1996; Gan and Amasino1997). The ensuing synthesis of particular proteins isresponsible for the degradation of essential macromol-ecules, profound alterations of cell structure and phys-iology, the mobilization of hydrolytic products to otherparts of the plant, and the eventual death of the organ(Thimann 1980; Nooden 1988; Guarente et al. 1998;Weaver et al. 1998). The chloroplast appears to be anearly target for senescence processes (Gepstein 1988).In order to understand the complex operationsinvolved in cell death, it is essential to identify theimportant components of its genetic program, even thosethat may not be strictly causal for senescence. Oneapproach is to isolate mRNAs that are up-regulatedduring senescence, and then predict their function byhomology to known gene products. The relationship of theseproteinstosenescenceeventuallycanbedeterminedby other molecular, cellular and biochemical techniques.With this objective in mind, dierential screening anddierential display techniques have resulted in theidenti®cation of a variety of senescence-associated genesthat provide greater insight into the processes related tocell death (Smart 1994; Buchanan-Wollaston 1997; Ganand Amasino 1997). This in turn led to the suggestionthat the regulation of senescence involves several inter-connected genetic pathways (Gan and Amasino 1997).We have been identifying other senescence-associatedgenes using an RNA ®ngerprinting technique based onthe method of ampli®ed restriction fragment polymor-phism (cDNA-AFLP) (Bachem et al. 1996). The advan-tage of this technique is that oligonucleotide adapterscan be used as primer sites for the polymerase chainreaction (PCR). As a result, the PCR conditions aremore stringent, and PCR artifacts that are common indierential display are decreased (Bachem et al. 1996).For this study, tobacco leaves were chosen as theexperimental material. They show a predictable progres-
Abbreviations: ACC
1-amino-cyclopropane-1-carboxylic acid;BA
benzyladenine; cDNA-AFLP
ampli®ed restriction frag-ment polymorphism-derived technique for RNA ®nger-printing;Chl
chlorophyll; ELIP
early light-induced protein; PCR
polymerase chain reaction
Correspondence to
: S. Gepstein;E-mail: gepstein@tx.technion.ac.il; Fax:+972-4-8225135Planta (2001) 212: 591±597
The early light-induced protein is also produced during leaf senescence of 
Nicotiana tabacum
L. Binyamin, M. Falah, V. Portnoy, E. Soudry, S. Gepstein
Faculty of Biology, Technion, Israel Institute of Technology, Haifa, 32000, IsraelReceived: 18 May 2000 /Accepted: 24 June 2000
 
sion of senescence from lower to upper leaves, and manyfactors involved in senescence have already been docu-mented. Furthermore, the loss of chlorophyll (Chl) is anearly, easily measured, and accepted criterion for senes-cence in tobacco (Aharoni and Liberman 1979). Finally,this plant is amenable to a range of molecular tech-niques, including the production of transgenic plants.We show here that a tobacco mRNA, whose putativeprotein product has a high homology to the early light-induced protein (ELIP), is up-regulated during leasenescence. This mRNA (called ELIP-TOB) appearsearlier after addition of 1-amino-cyclopropane-1-carboxylic acid (ACC), which stimulates senescence,and is prevented by benzyladenine (BA), which delayssenescence. Furthermore, the appearance of ELIP-TOBmRNA is dependent on light, and is accelerated bystresses such as anaerobiosis and drought even beforeChl losses are detected. Thus, we show for the ®rst timethat ELIP is not only produced during greening in theearly stages of leaf development, but also duringsenescence. We present the possibility that elevatedlevels of ELIP-TOB mRNA at this later stage may be aresult, at least in part, of stress perception by leaf cells.
Materials and methods
Plant material 
Tobacco (
Nicotiana tabacum
L. cv. SR1) plants were grown in soil-containing pots in the greenhouse at an average temperature of 25
°
C under a 16-h photoperiod maintained with ¯uorescent lights.The plants were watered with tap water every 2 d. For studies of arti®cialsenescence,fullyexpandedgreenleaveswereremovedfromplantsthatwereapproximately8weeksoldandthebaseoftheleavesinsertedintodistilledwateroraqueoussolutionsofACC(1 mM)orBA (0.1 mM). Anaerobic conditions were obtained by submergingdetached leaves from 8-week-old plants under water. Water stresswas accomplished by withholding water from 8-week-old plants for10 d before leaf removal. The progression of senescence wasdetermined by comparing Chl content of the experimental materialto that of green, fully expanded leaves using the method of Moran(1982). The various stages of senescence were designated as: G2,100% (Chl content); G1, 80%; GY, 60%, Y1, 50%; Y2, 25%.
Preparation of poly(A)
+
RNA and the synthesis of cDNA
Leaves were frozen in liquid nitrogen and stored at
)
80
°
C untiluse. Total RNA was extracted according to the method of Puissantand Houdebine (1990). The concentration of RNA was determinedspectrophotometrically and resolved on agarose gels to evaluatequality. Polyadenylated RNA was prepared using the PolyATractRNA Isolation System (Promega). Double-stranded DNA wassynthesized with a cDNA Synthesis Module (Amersham) with ananchored oligo dT
25
that enabled the production of a cDNA librarycontaining a high percentage of full-length cDNA clones. Theyields of cDNA were estimated by the incorporation of [
32
P]dATP.
Treatment of cDNA for AFLP analysis
Samples (100 ng) of double-stranded cDNA were digested withEco
RI 
and Mse
restriction enzymes (2.5 U each) and ligated toEco
RI 
/Mse
adapters as described in the AFLP Analysis System Ikit protocol (Gibco BRL). The ligated fragments were preampli®edby including a single selective nucleotide at the 3
¢
end (Eco
RI 
andMse
+ N) (where N represents A, C, G or T). This was followedby selective AFLP ampli®cation using Eco
RI 
and Mse
+ NNNprimers labeled by phosphorylating the 5
¢
end with [
c
-
33
P]ATP.Polymerase chain reaction was performed as follows: the ®rst cyclewas 30 s at 94
°
C, 30 s at65
°
Cand1 minat72
°
C.Inthefollowing12 cycles the annealing temperature was reduced by 0.7
°
C for eachcycle. The ®nal 23 cycles were performed using the followingtemperatures: 30 s at 94
°
C, 30 s at 56
°
C, and 1 min at 72
°
C.
Gel electrophoresis
The reaction mixtures of the PCR products were combined with anequal volume of 98% (v/v) formamide, 10 mM EDTA, 0.25%bromophenol blue, 0.25% xylene cyanol, heated for 3 min at 90
°
Cand immediately cooled on ice. A 2-
l
l portion of each sample wasresolved on a 6% (w/v) polyacrylamide sequencing gel. The PCRreaction products, using the same selective primers from young andsenescing leaves of tobacco, were resolved side by side. The gel wasthen dried and exposed to New Kodak BioMax MR ®lm overnightat room temperature.
Cloning of ampli®ed fragments
Senescence-associated bands were cut from the dried gel, soaked in50
l
l sterile water and heated for 2 h at 65
°
C. After a briecentrifugation, 10
l
l of the supernatant was transferred to anothertube. Re-ampli®cation of the recovered fragment was performedwiththesameprimersinitiallyusedfortheselectiveAFLPreactions.The temperature pro®le for PCR (30 cycles) was as follows: 30 s at94
°
C, 30 s at 56
°
C, and 1 min at 72
°
C. The PCR products wereseparated on a 2% (w/v) agarose gel, then eluted and ligated topUC57 vector in order to transform competent DH5 alpha cells. Toverify that the isolated fragment was indeed senescence-associated,it was utilized as a probe for Northern blot analysis.
Hybridization of RNA blots
Fifteen micrograms of total RNA from young and senescing leaveswas denatured with glyoxal, subjected to electrophoresis on a 1%(w/v) agarose gel, and transferred to a Zeta-Probe GT membrane(Bio-Rad) in 20
´
SSC (20
´
SSC
3 M NaCl, 0.3 M sodiumcitrate, pH 8.0) as instructed. For preparation of probes, plasmid-transformed cells containing the DNA fragment of interest werecultured overnight in 5 ml LB (Sambrook et al. 1989) thatcontained 100
l
g/ml ampicillin at 37
°
C. After plasmid isolation,the fragment was then ampli®ed under the same conditions as thosedescribed for the ampli®cation of DNA fragments from dried gels.The fragment was eluted from the agarose gel and labeled by therandom primer labeling technique using [
32
P]dATP as described inSambrooketal.(1989). HybridizationofRNA blotswas performedovernight in a mixture of 6
´
SSC, 0.5% (w/v) SDS, 50% (v/v)formamide, 0.1 mg/ml of sonicated and denatured salmon spermDNA, and 2
´
10
6
cpm/ml of probe at 60
°
C. After hybridization,the blot was washed successively with 2
´
SSC, 0.1% (w/v) SDS for15 min at 55
°
C, and1
´
SSC, 0.1%(w/v) SDS for15 min at55
°
C,and 0.5
´
SSC, 0.1%(w/v) SDS for 15 min at 55
°
C.
Immunoblots
Fifty micrograms of total leaf protein in buer containing SDS wasseparated by PAGE and blotted as described previously (Dumbro and Gepstein 1993). The blots were exposed to antibodies elicitedagainst tobacco ELIP (produced and provided by Prof. K.Kloppstech), washed, and then treated with goat anti-rabbit IgGconjugated to peroxidase (BioRad). Binding was visualized bytreatment with peroxidase substrate.592 L. Binyamin et al.: Production of early light-induced protein during senescence
 
Results
Using the cDNA-AFLP technique, we isolated andcloned a 247-bp cDNA that binds to an mRNA of approximately 800 bp and that increases during senes-cence. This cDNA is a fragment with a high similarity(79%) to the ELIP family of proteins, nuclear-encodedchloroplast proteins, whose appearance is dependent onthe presence of light (Meyer and Kloppstech 1984;Grimm and Kloppstech 1987). The region of thededuced ELIP amino acid sequence from tobacco ishomologous to the most conserved region of ELIPsfrom pea, soybean and
Arabidopsis
(Fig. 1). Because theamino acid sequence has a high homology to ELIPs, wecalled the isolated fragment ELIP-TOB.As shown in Fig. 2A, the ELIP-TOB cDNA boundto an mRNA that appeared when Chl levels haddecreased by about 40% (GY). The mRNA levelsincreased until Chl levels were 50% or less than theoriginal value (Y1). A northern blot was also performedusing RNA from detached leaves that began to senescewithin 1 to 3 d (Fig. 2B). The trend is similar to that of the intact leaves that age more slowly, but the ELIP-TOB mRNA appeared only 1 d after detachment, evenbefore Chl levels began to decline. In fact, it was possibleto detect an increase in the mRNA only 4 h after leaf removal (see Fig. 4). As Chl content decreased, therewas a striking enhancement of this mRNA (Fig. 2B).To determine if the ELIP protein was producedduring leaf senescence, antibodies were obtained inorder to run immunoblots. The results (Fig. 2C) indicatethat ELIP protein is detectable in the tobacco leavesafter Chl levels have decreased about 40%.To test whether the appearance of ELIP-TOB mRNAduringsenescenceisdependentonlight,detachedtobaccoleaveswereagedinthedark,andthesteady-statelevelsof this mRNA were estimated by Northern blots (Fig. 3A).There was no detectable mRNA from the ELIP-TOBgene in leaves incubated in the dark compared with thosein the light, even though the dark treatment resulted in amore rapid loss of chlorophyll. This experiment stronglysuggests that the increased levels of ELIP-TOB mRNAduring senescence are dependent on light.To further examine the light requirement for thesenescence-induced up-regulation of ELIP-TOB, intacttobacco plants were transferred todarkness for20 d,andthe ELIP-TOB mRNA levels of senescing leaves fromthese plants were compared with senescing leaves fromsimilarly aged plants that remained in the light (Fig. 3B).After 20 d in the dark, the mRNA for ELIP-TOB couldnot be detected in the senescent leaves, but it was seen insenescent leaves of plants in the light even though thelight-treated leaves chosen showed the same degree of Chl loss as those in the dark. In another experiment,detached leaves were incubated in the light until the GYstageandthenplacedinthedarkfor2 dlonger(Fig. 3C).Although ELIP-TOB mRNA was present at the GYstage (Fig. 2B), the mRNA was undetectable after darkincubation even though only 50% of the Chl remained(stage Y1); ELIP-TOB mRNA was clearly present at thissame stage in light-treated leaves (Fig. 3C).We also studied the eect of certain hormones thatregulate senescence on the levels of ELIP-TOB mRNAin green, detached leaves. A northern blot (Fig. 4)showed that treatment with ACC, the precursor of ethylene, clearly increased the mRNA after only 2 h,and the level remained high for 10 d. On the other hand,the synthetic cytokinin, BA, delayed the increase inELIP-TOB mRNA until about day 3, and only at day 5did the level of this mRNA approach that of thecontrol.Expression of ELIPs has been associated with certainstresses (Adamska et al. 1992; Potter and Kloppstech1993; Adamska 1997). To compare mRNA levels of ELIP-TOB with those of other plants under stress, weexposed detached tobacco leaves to anaerobic condi-tions (Fig. 5A). Chlorophyll levels decreased at a slowerrate than leaves in air, as seen previously for pathogen-induced programmed cell death (Mittler et al. 1996), butsteady-state levels of ELIP-TOB mRNA increasedmarkedly by 1 d after the oxygen stress and remainedelevated. Levels of ELIP-TOB mRNA in controlsreached a maximum only at day 5 (Figs. 2B, 4).The plants were also subjected to a drought stress(Fig. 5B). There was a marked increase in ELIP-TOBmRNA in leaves of plants without water for 10 d,whereas this mRNA was undetectable in control leavesof the same age from plants that had sucient water.The water stress resulted in an elevation of ELIP-TOBmRNA levels before Chl decreases could be measured.
Fig. 1.
Alignment of ELIP amino acid sequences. Amino acidsequences deduced from the corresponding partial cDNA sequenceof ELIP-TOB are compared with the ®rst transmembrane domain of ELIP proteins from soybean (
Soy
) (accession number JC 5876), pea(
Pea
) (accession numbers P11432, SO1056), and
Arabidopsis
(
Arb
)(accession number 88391). Also shown is the sequence of Sep1 from
Arabidopsis
(
Arb-Sep1
) (accession number AAF61625).
Dashes
indicate the gaps inserted to allow optimal alignment. The
blackboxes
indicate identical residues and
gray boxes
indicate conservativesubstitutions Alignment of ELIPs and Sep was carried out using themultiple alignment program, CLUSTLAWL. Binyamin et al.: Production of early light-induced protein during senescence 593
of 00

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